fbpx
Wikipedia

Organoid

April 14, 2024

For Organoids appearing in an anime series, see Zoids § Organoids.

An organoid is a miniaturised and simplified version of an organ produced in vitro in three dimensions that mimics the key functional, structural and biological complexity of that organ.[1] They are derived from one or a few cells from a tissue, embryonic stem cells or induced pluripotent stem cells, which can self-organize in three-dimensional culture owing to their self-renewal and differentiation capacities. The technique for growing organoids has rapidly improved since the early 2010s, and The Scientist names it as one of the biggest scientific advancements of 2013.[2] Scientists and engineers use organoids to study development and disease in the laboratory, drug discovery and development in industry,[3] personalized diagnostics and medicine, gene and cell therapies, tissue engineering and regenerative medicine.

Intestinal organoid grown from Lgr5+ stem cells

History edit

Attempts to create organs in vitro started with one of the first dissociation-reaggregation experiments[4] where Henry Van Peters Wilson demonstrated that mechanically dissociated sponge cells can reaggregate and self-organize to generate a whole organism.[5] In the subsequent decades, multiple labs were able to generate different types of organs[4] in vitro through the dissociation and reaggregation of organ tissues obtained from amphibians[6] and embryonic chicks.[7] The formation of first tissue-like colonies in vitro was observed for the first time by co-culturing keratinocytes and 3T3 fibroblasts.[8] The phenomena of mechanically dissociated cells aggregating and reorganizing to reform the tissue they were obtained from subsequently led to the development of the differential adhesion hypothesis by Malcolm Steinberg.[4] With the advent of the field of stem cell biology, the potential of stem cells to form organs in vitro was realized early on with the observation that when stem cells form teratomas or embryoid bodies, the differentiated cells can organize into different structures resembling those found in multiple tissue types.[4] The advent of the field of organoids, started with a shift from culturing and differentiating stem cells in two dimensional (2D) media, to three dimensional (3D) media to allow for the development of the complex 3-dimensional structures of organs.[4] Utilization of 3D media culture media methods for the structural organization was made possible with the development of extracellular matrices (ECM).[9] In the late 1980s, Bissell and colleagues showed that a laminin rich gel can be used as a basement membrane for differentiation and morphogenesis in cell cultures of mammary epithelial cells.[10][11] Since 1987, researchers have devised different methods for 3D culturing, and were able to utilize different types of stem cells to generate organoids resembling a multitude of organs.[4] In the 1990s, in addition to their role in physical support, the role of ECM components in gene expression by their interaction with integrin-based focal adhesion pathways was reported.[12] In 2006, Yaakov Nahmias and David Odde showed the self-assembly of vascular liver organoid maintained for over 50 days in vitro.[13] In 2008, Yoshiki Sasai and his team at RIKEN institute demonstrated that stem cells can be coaxed into balls of neural cells that self-organize into distinctive layers.[14] In 2009 the Laboratory of Hans Clevers at Hubrecht Institute and University Medical Center Utrecht, Netherlands, showed that single LGR5-expressing intestinal stem cells self-organize to crypt-villus structures in vitro without necessity of a mesenchymal niche, making them the first organoids.[15] In 2010, Mathieu Unbekandt & Jamie A. Davies demonstrated the production of renal organoids from murine fetus-derived renogenic stem cells.[16] In 2014, Qun Wang and co-workers engineered collagen-I and laminin based gels and synthetic foam biomaterials for the culture and delivery of intestinal organoids[17] and encapsulated DNA-functionalized gold nanoparticles into intestinal organoids to form an intestinal Trojan horse for drug delivery and gene therapy.[18] Subsequent reports showed significant physiological function of these organoids in vitro[19] and in vivo.[20][21]

Other significant early advancements included in 2013, Madeline Lancaster at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences established a protocol starting from pluripotent stem cells to generate cerebral organoids that mimic the developing human brain's cellular organization.[22] Meritxell Huch and Craig Dorrell at Hubrecht Institute and University Medical Center Utrecht demonstrated that single Lgr5+ cells from damaged mouse liver can be clonally expanded as liver organoids in Rspo1-based culture medium over several months.[23] In 2014, Artem Shkumatov et al. at the University of Illinois at Urbana-Champaign demonstrated that cardiovascular organoids can be formed from ES cells through modulation of the substrate stiffness, to which they adhere. Physiological stiffness promoted three-dimensionality of EBs and cardiomyogenic differentiation.[24] In 2015, Takebe et al. demonstrated a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell-derived tissue-specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells. They suggested that the less mature tissues, or organ buds, generated through the self-organized condensation principle might be the most efficient approach toward the reconstitution of mature organ functions after transplantation, rather than condensates generated from cells of a more advanced stage.[25]

Properties edit

Lancaster and Knoblich[4] define an organoid as a collection of organ-specific cell types that develops from stem cells or organ progenitors, self-organizes through cell sorting and spatially restricted lineage commitment in a manner similar to in vivo, and exhibits the following properties:

  • it has multiple organ-specific cell types;
  • it is capable of recapitulating some specific function of the organ (e.g. contraction, neural activity, endocrine secretion, filtration, excretion);
  • its cells are grouped together and spatially organized, similar to an organ.

Process edit

Organoid formation generally requires culturing the stem cells or progenitor cells in a 3D medium.[4] Stem cells have the ability to self-renew and differentiate into various cell subtypes, and they enable understanding the processes of development and disease progression.[26] Therefore organoids derived from stem cells enable studying biology and physiology at the organ level.[27] The 3D medium can be made using an extracellular matrix hydrogel such as Matrigel or Cultrex BME, which is a laminin-rich extracellular matrix that is secreted by the Engelbreth-Holm-Swarm tumor line.[28] Organoid bodies can then be made through embedding stem cells in the 3D medium.[4] When pluripotent stem cells are used for the creation of the organoid, the cells are usually, but not all the time, allowed to form embryoid bodies.[4] Those embryoid bodies are then pharmacologically treated with patterning factors to drive the formation of the desired organoid identity.[4] Organoids have also been created using adult stem cells extracted from the target organ, and cultured in 3D media.[29]

Biochemical cues have been incorporated in 3D organoid cultures and with exposure of morphogenes, morphogen inhibitors, or growth factors, organoid models can be developed using embryonic stem cells (ESCs) or adult stem cells (ASCs). Vascularization techniques can be utilized to embody microenvironments that are close to their counterparts, physiologically. Vasculature systems that can facilitate oxygen or nutrients to the inner mass of organoids can be achieved through microfluidic systems, vascular endothelial growth factor delivery systems, and endothelial cell-coated modules.[9] With patient-derived induced pluripotent stem cells (iPSCs)[30] and CRISPR/Cas-based genome editing[31] technologies, genome-edited or mutated pluripotent stem cells (PSCs) with altered signaling cues can be generated to control intrinsic cues within organoids.

Types edit

A multitude of organ structures have been recapitulated using organoids.[4] This section aims to outline the state of the field as of now through providing an abridged list of the organoids that have been successfully created, along with a brief outline based on the most recent literature for each organoid, and examples of how it has been utilized in research.

Cerebral organoid edit

A cerebral organoid describes artificially grown, in vitro, miniature organs resembling the brain. Cerebral organoids are created by culturing human pluripotent stem cells in a three-dimensional structure using rotational bioreactor and develop over the course of months.[22] The procedure has potential applications in the study of brain development, physiology and function. Cerebral organoids may experience "simple sensations" in response to external stimulation and neuroscientists are among those expressing concern that such organs could develop sentience. They propose that further evolution of the technique needs to be subject to a rigorous oversight procedure.[32][33][34] In 2023, researchers have built a hybrid biocomputer that combines a laboratory-grown human brain organoids with conventional circuits, and can complete tasks such as voice recognition.[35] Cerebral Organoids are currently being used to research and develop Organoid Intelligence (OI) technologies.[36]

Gastrointestinal organoid edit

Gastrointestinal organoids refer to organoids that recapitulate structures of the gastrointestinal tract. The gastrointestinal tract arises from the endoderm, which during development forms a tube that can be divided in three distinct regions, which give rise to, along with other organs, the following sections of the gastrointestinal tract:[4]

  1. The foregut gives rise to the oral cavity and the stomach
  2. The midgut gives rise to the small intestines and the ascending colon
  3. The hindgut gives rise to the rectum and the rest of the colon

Organoids have been created for the following structures of the gastrointestinal tract:

Intestinal organoid edit

Intestinal organoids[15] have thus far been among the gut organoids generated directly from intestinal tissues or pluripotent stem cells.[4] One way human pluripotent stem cells can be driven to form intestinal organoids is through first the application of activin A to drive the cells into a mesoendodermal identity, followed by the pharmacological upregulation of Wnt3a and Fgf4 signaling pathways as they have been demonstrated to promote posterior gut fate.[4] Intestinal organoids have also been generated from intestinal stem cells, extracted from adult tissue and cultured in 3D media.[29] These adult stem cell-derived organoids are often referred to as enteroids or colonoids, depending on their segment of origin, and have been established from both the human and murine intestine.[15][37][38] Intestinal organoids consist of a single layer of polarized intestinal epithelial cells surrounding a central lumen. As such, recapitulate the crypt-villus structure of the intestine, by recapitulating its function, physiology and organization, and maintaining all the cell types found normally in the structure including intestinal stem cells.[4] Thus, intestinal organoids are a valuable model to study intestinal nutrient transport,[39][40] drug absorption and delivery,[41][42] nanomaterials and nanomedicine,[43][44] incretin hormone secretion,[45][46] and infection by various enteropathogens.[47][48] For example, Qun Wang's team rationally designed artificial virus nanoparticles as oral drug delivery vehicles (ODDVs) with gut organoid-derived mucosal models[49] and demonstrated a new concept of using newly established colon organoids as tools for high-throughput drug screening, toxicity testing, and oral drug development.[50] Intestinal organoids also recapitulate the crypt-Villus structure to such a high degree of fidelity that they have been successfully transplanted to mouse intestines, and are hence highly regarded as a valuable model for research.[4] One of the fields of research that intestinal organoids have been utilized is that of stem cell niche. Intestinal organoids were used to study the nature of the intestinal stem cell niche, and research done with them demonstrated the positive role IL-22 has in maintaining in intestinal stem cells,[51] along with demonstrating the roles of other cell types like neurons and fibroblasts in maintenance of intestinal stem cells.[29] In the field of infection biology, different intestinal organoid-based model systems have been explored. On one hand, organoids can be infected in bulk by simply mixing them with the enteropathogen of interest.[52] However, to model infection via a more natural route starting from the intestinal lumen, microinjection of the pathogen is required.[53][54] In addition, the polarity of intestinal organoids can be inverted,[55] and they can even be dissociated into single cells and cultured as 2D monolayers[56][57] in order to make both the apical and basolateral sides of the epithelium more easily accessible. Intestinal organoids have also demonstrated therapeutic potential.[58]

 
An intestinal organoid (Minigut) grows up in 7 days. The scale bars are 200 μm.

In order to more accurately recapitulate the intestine in vivo, co-cultures of intestinal organoids and immune cells have been developed.[57] Furthermore, organ-on-a-chip models combine intestinal organoids with other cell types such as endothelial or immune cells as well as peristaltic flow.[59][60]

Gastric organoid edit

Gastric organoids recapitulate at least partly the physiology of the stomach. Gastric organoids have been generated directly from pluripotent stem cells through the temporal manipulation of the FGF, WNT, BMP, retinoic acid and EGF signalling pathways in three-dimensional culture conditions.[61] Gastric organoids have also been generated using LGR5 expressing stomach adult stem cells.[62] Gastric organoids have been used as model for the study of cancer[63][64] along with human disease[61] and development.[61] For example, one study[64] investigated the underlying genetic alterations behind a patient's metastatic tumor population, and identified that unlike the patient's primary tumor, the metastasis had both alleles of the TGFBR2 gene mutated. To further assess the role of TGFBR2 in the metastasis, the investigators created organoids where TGFBR2 expression is knocked down, through which they were able to demonstrate that reduced TGFBR2 activity leads to invasion and metastasis of cancerous tumors both in vitro and in vivo.

Lingual organoid edit

Lingual organoids are organoids that recapitulate, at least partly, aspects of the tongue physiology. Epithelial lingual organoids have been generated using BMI1 expressing epithelial stem cells in three-dimensional culture conditions through the manipulation of EGF, WNT, and TGF-β.[65] This organoid culture, however, lacks taste receptors, as these cells do not arise from Bmi1 expressing epithelial stem cells.[65] Lingual taste bud organoids containing taste cells, however, have been created using the LGR5+ or CD44+ stem/progenitor cells of circumvallate (CV) papilla tissue.[66] These taste bud organoids have been successfully created both directly from isolated Lgr5- or LGR6-expressing taste stem/progenitor cells.[67] and indirectly, through the isolation, digestion, and subsequent culturing of CV tissue containing Lgr5+ or CD44+ stem/progenitor cells.[66]

Other edit

Thymic organoids recapitulate at least partly the architecture and stem-cell niche functionality of the thymus,[71] which is a lymphoid organ where T cells mature. Thymic organoids have been generated through the seeding of thymic stromal cells in 3-dimensional culture.[71] Thymic organoids seem to successfully recapitulate the thymus' function, as co-culturing human hematopoietic or bone marrow stem cells with mouse thymic organoids resulted in the production of T-cells.[71]
  • Testicular organoid[72]
  • Prostate organoid[73]
  • Hepatic organoid.[74] A recent study showed the usefulness of the technology for identifying novel medication for the treatment of hepatitis E as it allows to allows to recapitulate the entire viral life cycle.[75]
  • Pancreatic organoid[76][77][78][79]
Recent advances in cell repellent microtiter plates has allowed rapid, cost-effective screening of large small molecule drug like libraries against 3D models of pancreas cancer. These models are consistent in phenotype and expression profiles with those found in the lab of Dr. David Tuveson.

3D organoid models of brain cancer derived from either patient derived explants (PDX) or direct from cancer tissue is now easily achievable and affords high-throughput screening of these tumors against the current panel of approved drugs form around the world.

Self-assembled cell aggregates consisting of BMECs, astrocytes, and pericytes are emerging as a potential alternative to transwell and microfluidic models for certain applications. These organoides can generate many features of the BBB, such as the expression of tight junctions, molecular transporters, and drug efflux pumps, and can therefore be used to model drug transport across the BBB. Also, they can serve as a model for evaluating the interactions between the BBB and adjacent brain tissue and provide a platform for understanding the combined abilities of a new drug to overcome the BBB and its effect on brain tissue. In addition, such models are highly scalable and easier to manufacture and operate than microfluidic devices. However, they have limited ability to reconstruct the morphology and physiology of the BBB and are unable to simulate physiological flow and shear stress.

Basic research edit

Organoids enable to study how cells interact together in an organ, their interaction with their environment, how diseases affect them and the effect of drugs. In vitro culture makes this system easy to manipulate and facilitates their monitoring. While organs are difficult to culture because their size limits the penetration of nutrients, the small size of organoids limits this problem. On the other hand, they do not exhibit all organ features and interactions with other organs are not recapitulated in vitro. While research on stem cells and regulation of stemness was the first field of application of intestinal organoids,[15] they are now also used to study e.g. uptake of nutrients, drug transport and secretion of incretin hormones.[102] This is of great relevance in the context of malabsorption diseases as well as metabolic diseases such as obesity, insulin resistance, and diabetes.

Models of disease edit

Organoids provide an opportunity to create cellular models of human disease, which can be studied in the laboratory to better understand the causes of disease and identify possible treatments. The power of organoids in this regard was first shown for a genetic form of microcephaly, where patient cells were used to make cerebral organoids, which were smaller and showed abnormalities in early generation of neurons.[22] In another example, the genome editing system called CRISPR was applied to human pluripotent stem cells to introduce targeted mutations in genes relevant to two different kidney diseases, polycystic kidney disease and focal segmental glomerulosclerosis.[83] These CRISPR-modified pluripotent stem cells were subsequently grown into human kidney organoids, which exhibited disease-specific phenotypes. Kidney organoids from stem cells with polycystic kidney disease mutations formed large, translucent cyst structures from kidney tubules. When cultured in the absence of adherent cues (in suspension), these cysts reached sizes of 1 cm in diameter over several months.[103] Kidney organoids with mutations in a gene linked to focal segmental glomerulosclerosis developed junctional defects between podocytes, the filtering cells affected in that disease.[104] Importantly, these disease phenotypes were absent in control organoids of identical genetic background, but lacking the CRISPR mutations.[83][103][104] Comparison of these organoid phenotypes to diseased tissues from mice and humans suggested similarities to defects in early development.[103][104]

As first developed by Takahashi and Yamanaka in 2007, induced pluripotent stem cells (iPSC) can also be reprogrammed from patient skin fibroblasts.[105] These stem cells carry the exact genetic background of the patient including any genetic mutations which might contribute to the development of human disease. Differentiation of these cells into kidney organoids has been performed from patients with Lowe Syndrome due to ORCL1 mutations.[106] This report compared kidney organoids differentiated from patient iPSC to unrelated control iPSC and demonstrated an inability of patient kidney cells to mobilise transcription factor SIX2 from the golgi complex.[106] Because SIX2 is a well characterised marker of nephron progenitor cells in the cap mesenchyme, the authors concluded that renal disease frequently seen in Lowe Syndrome (global failure of proximal tubule reabsorption or renal Fanconi syndrome) could be related to alteration in nephron patterning arising from nephron progenitor cells lacking this important SIX2 gene expression.[106]

Other studies have used CRISPR gene editing to correct the patient's mutation in the patient iPSC cells to create an isogenic control, which can be performed simultaneously with iPSC reprogramming.[107][108][109] Comparison of a patient iPSC derived organoid against an isogenic control is the current gold standard in the field as it permits isolation of the mutation of interest as the only variable within the experimental model.[110] In one such report, kidney organoids derived from iPSC of a patient with Mainzer-Saldino Syndrome due to compound heterozygous mutations in IFT140 were compared to an isogenic control organoid in which an IFT140 variant giving rise to a non-viable mRNA transcript was corrected by CRISPR.[108] Patient kidney organoids demonstrated abnormal ciliary morphology consistent with existing animal models which was rescued to wild type morphology in the gene corrected organoids.[108] Comparative transcriptional profiling of epithelial cells purified from patient and control organoids highlighted pathways involved in cell polarity, cell-cell junctions and dynein motor assembly, some of which had been implicated for other genotypes within the phenotypic family of renal ciliopathies.[108] Another report utilising an isogenic control demonstrated abnormal nephrin localisation in the glomeruli of kidney organoids generated from a patient with congenital nephrotic syndrome.[109]

Things such as epithelial metabolism can also be modelled.[111]

Personalised medicine edit

Intestinal organoids grown from rectal biopsies using culture protocols established by the Clevers group have been used to model cystic fibrosis,[112] and led to the first application of organoids for personalised treatment.[113] Cystic fibrosis is an inherited disease that is caused by gene mutations of the cystic fibrosis transmembrane conductance regulator gene that encodes an epithelial ion channel necessary for healthy epithelial surface fluids. Studies by the laboratory of Jeffrey Beekman (Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands) described in 2013 that stimulation of colorectal organoids with cAMP-raising agonists such as forskolin or cholera toxin induced rapid swelling of organoids in a fully CFTR dependent manner.[112] Whereas organoids from non-cystic fibrosis subjects swell in response to forskolin as a consequence of fluid transport into the organoids' lumens, this is severely reduced or absent in organoids derived from people with cystic fibrosis. Swelling could be restored by therapeutics that repair the CFTR protein (CFTR modulators), indicating that individual responses to CFTR modulating therapy could be quantitated in a preclinical laboratory setting. Schwank et al. also demonstrated that the intestinal cystic fibrosis organoid phenotype could be repaired by CRISPR-Cas9 gene editing in 2013.[114]

Follow-up studies by Dekkers et al. in 2016 revealed that quantitative differences in forskolin-induced swelling between intestinal organoids derived from people with cystic fibrosis associate with known diagnostic and prognostic markers such as CFTR gene mutations or in vivo biomarkers of CFTR function.[113] In addition, the authors demonstrated that CFTR modulator responses in intestinal organoids with specific CFTR mutations correlated with published clinical trial data of these treatments. This led to preclinical studies where organoids from patients with extremely rare CFTR mutations for who no treatment was registered were found to respond strongly to a clinically available CFTR modulator. The suggested clinical benefit of treatment for these subjects based on the preclinical organoid test was subsequently confirmed upon clinical introduction of treatment by members of the clinical CF center under supervision of Kors van der Ent (Department of Paediatric Pulmonology, Wilhelmina Children's Hospital, University Medical Center Utrecht, The Netherlands). These studies show for the first time that organoids can be used for the individual tailoring of therapy or personalised medicine.

Organoid transplants edit

The first successful transplantation of an organoid into a human, a patient with ulcerative colitis whose cells were used for the organoid, was carried out in 2022.[115][116]

As a model for developmental biology edit

Organoids offer researchers an exceptional model to study developmental biology.[117] Since the identification of pluripotent stem cells, there have been great advancements in directing pluripotent stem cells fate in vitro using 2D cultures.[117] These advancements in PSC fate direction, coupled with the advancements in 3D culturing techniques allowed for the creation of organoids that recapitulate the properties of various specific subregions of a multitude of organs.[117] The use of these organoids has thus greatly contributed to expanding our understanding of the processes of organogenesis, and the field of developmental biology.[117] In central nervous system development, for example, organoids have contributed to our understanding of the physical forces that underlie retinal cup formation.[117][118] More recent work has extended cortical organoid growth periods extensively and at nearly a year under specific differentiation conditions, the organoids persist and have some features of human fetal development stages.[119]

See also edit

References edit

  1. ^ Zhao Z, Chen X, Dowbaj AM, Sljukic A, Bratlie K, Lin L, Fong ELS, Balachander GM, Chen Z, Soragni A, Huch M, Zeng YA, Wang Q, Yu H. Organoids. Nature Reviews Methods Primers 2, 94 (2022). https://doi.org/10.1038/s43586-022-00174-y
  2. ^ Grens K (December 24, 2013). "2013's Big Advances in Science". The Scientist. Retrieved 26 December 2013.
  3. ^ Hans Clevers, Asher Mullard. Mini-organs attract big pharma. Nature Reviews Drug Discovery (16 February 2023). https://doi.org/10.1038/d41573-023-00030-y
  4. ^ a b c d e f g h i j k l m n o p q Lancaster MA, Knoblich JA (July 2014). "Organogenesis in a dish: modeling development and disease using organoid technologies". Science. 345 (6194): 1247125. doi:10.1126/science.1247125. PMID 25035496. S2CID 16105729.
  5. ^ Wilson HV (June 1907). "A new method by which sponges may be artificially reared". Science. 25 (649): 912–5. Bibcode:1907Sci....25..912W. doi:10.1126/science.25.649.912. PMID 17842577.
  6. ^ Holtfreter J (1944). "Experimental studies on the development of the pronephros". Rev. Can. Biol. 3: 220–250.
  7. ^ Weiss P, Taylor AC (September 1960). "Reconstitution of complete organs from single-cell suspensions of chick embryos in advanced stages of differentiation". Proceedings of the National Academy of Sciences of the United States of America. 46 (9): 1177–85. Bibcode:1960PNAS...46.1177W. doi:10.1073/pnas.46.9.1177. PMC 223021. PMID 16590731.
  8. ^ Rheinwald, James G.; Green, Howard (November 1975). "Formation of a keratinizing epithelium in culture by a cloned cell line derived from a teratoma". Cell. 6 (3): 317–330. doi:10.1016/0092-8674(75)90183-x. ISSN 0092-8674. PMID 1052770. S2CID 28185779.
  9. ^ a b Yi, Sang Ah; Zhang, Yixiao; Rathnam, Christopher; Pongkulapa, Thanapat; Lee, Ki-Bum (November 2021). "Bioengineering Approaches for the Advanced Organoid Research". Advanced Materials. 33 (45): e2007949. Bibcode:2021AdM....3307949Y. doi:10.1002/adma.202007949. ISSN 0935-9648. PMC 8682947. PMID 34561899.
  10. ^ Li, M L; Aggeler, J; Farson, D A; Hatier, C; Hassell, J; Bissell, M J (January 1987). "Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells". Proceedings of the National Academy of Sciences. 84 (1): 136–140. Bibcode:1987PNAS...84..136L. doi:10.1073/pnas.84.1.136. ISSN 0027-8424. PMC 304157. PMID 3467345.
  11. ^ Barcellos-Hoff, M. H.; Aggeler, J.; Ram, T. G.; Bissell, M. J. (1989-02-01). "Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane". Development. 105 (2): 223–235. doi:10.1242/dev.105.2.223. ISSN 0950-1991. PMC 2948482. PMID 2806122.
  12. ^ Streuli, C H; Schmidhauser, C; Bailey, N; Yurchenco, P; Skubitz, A P; Roskelley, C; Bissell, M J (1995-05-01). "Laminin mediates tissue-specific gene expression in mammary epithelia". The Journal of Cell Biology. 129 (3): 591–603. doi:10.1083/jcb.129.3.591. ISSN 0021-9525. PMC 2120432. PMID 7730398.
  13. ^ Nahmias Y, Schwartz RE, Hu WS, Verfaillie CM, Odde DJ (June 2006). "Endothelium-mediated hepatocyte recruitment in the establishment of liver-like tissue in vitro". Tissue Engineering. 12 (6): 1627–38. doi:10.1089/ten.2006.12.1627. PMID 16846358.
  14. ^ Yong E (August 28, 2013). "Lab-Grown Model Brains". The Scientist. Retrieved 26 December 2013.
  15. ^ a b c d e Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, et al. (May 2009). "Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche". Nature. 459 (7244): 262–5. Bibcode:2009Natur.459..262S. doi:10.1038/nature07935. PMID 19329995. S2CID 4373784.
  16. ^ a b Unbekandt M, Davies JA (March 2010). "Dissociation of embryonic kidneys followed by reaggregation allows the formation of renal tissues". Kidney International. 77 (5): 407–16. doi:10.1038/ki.2009.482. PMID 20016472.
  17. ^ Peng H, Poovaiah N, Forrester M, Cochran E, Wang Q. Ex Vivo Culture of Primary Intestinal Stem Cells in Collagen Gels and Foams. ACS Biomaterials Science & Engineering. 2014 Dec 2;1(1):37–42. https://doi.org/10.1021/ab500041d. PMID: 33435081.
  18. ^ Peng H, Wang C, Xu X, Yu C, Wang Q. An intestinal Trojan horse for gene delivery. Nanoscale. 2015 Jan 6;7(10):4354–4360. https://doi.org/10.1039/C4NR06377E. PMID: 25619169.
  19. ^ Lawrence ML, Chang CH, Davies JA (March 2015). "Transport of organic anions and cations in murine embryonic kidney development and in serially-reaggregated engineered kidneys". Scientific Reports. 5: 9092. Bibcode:2015NatSR...5E9092L. doi:10.1038/srep09092. PMC 4357899. PMID 25766625.
  20. ^ Xinaris C, Benedetti V, Rizzo P, Abbate M, Corna D, Azzollini N, et al. (November 2012). "In vivo maturation of functional renal organoids formed from embryonic cell suspensions". Journal of the American Society of Nephrology. 23 (11): 1857–68. doi:10.1681/ASN.2012050505. PMC 3482737. PMID 23085631.
  21. ^ Yui, S., Nakamura, T., Sato, T. et al. Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell. Nature Medicine 18, 618–623 (2012). https://doi.org/10.1038/nm.2695
  22. ^ a b c Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, et al. (September 2013). "Cerebral organoids model human brain development and microcephaly". Nature. 501 (7467): 373–9. Bibcode:2013Natur.501..373L. doi:10.1038/nature12517. PMC 3817409. PMID 23995685.
  23. ^ Huch, M., Dorrell, C., Boj, S. et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 494, 247–250 (2013). https://doi.org/10.1038/nature11826
  24. ^ Shkumatov A, Baek K, Kong H (2014). "Matrix rigidity-modulated cardiovascular organoid formation from embryoid bodies". PLOS ONE. 9 (4): e94764. Bibcode:2014PLoSO...994764S. doi:10.1371/journal.pone.0094764. PMC 3986240. PMID 24732893.
  25. ^ Takebe T, Enomura M, Yoshizawa E, Kimura M, Koike H, Ueno Y, et al. (May 2015). "Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation". Cell Stem Cell. 16 (5): 556–65. doi:10.1016/j.stem.2015.03.004. PMID 25891906.
  26. ^ Murry, Charles E.; Keller, Gordon (February 2008). "Differentiation of Embryonic Stem Cells to Clinically Relevant Populations: Lessons from Embryonic Development". Cell. 132 (4): 661–680. doi:10.1016/j.cell.2008.02.008. ISSN 0092-8674. PMID 18295582.
  27. ^ Choudhury, Deepak; Ashok, Aswathi; Naing, May Win (March 2020). "Commercialization of Organoids". Trends in Molecular Medicine. 26 (3): 245–249. doi:10.1016/j.molmed.2019.12.002. ISSN 1471-4914. PMID 31982341. S2CID 210922708.
  28. ^ Li ML, Aggeler J, Farson DA, Hatier C, Hassell J, Bissell MJ (January 1987). "Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells". Proceedings of the National Academy of Sciences of the United States of America. 84 (1): 136–40. Bibcode:1987PNAS...84..136L. doi:10.1073/pnas.84.1.136. PMC 304157. PMID 3467345.
  29. ^ a b c Pastuła A, Middelhoff M, Brandtner A, Tobiasch M, Höhl B, Nuber AH, et al. (2016). "Three-Dimensional Gastrointestinal Organoid Culture in Combination with Nerves or Fibroblasts: A Method to Characterize the Gastrointestinal Stem Cell Niche". Stem Cells International. 2016: 3710836. doi:10.1155/2016/3710836. PMC 4677245. PMID 26697073.
  30. ^ Takahashi, Kazutoshi; Yamanaka, Shinya (August 2006). "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors". Cell. 126 (4): 663–676. doi:10.1016/j.cell.2006.07.024. hdl:2433/159777. ISSN 0092-8674. PMID 16904174.
  31. ^ Ran, F Ann; Hsu, Patrick D; Wright, Jason; Agarwala, Vineeta; Scott, David A; Zhang, Feng (2013-10-24). "Genome engineering using the CRISPR-Cas9 system". Nature Protocols. 8 (11): 2281–2308. doi:10.1038/nprot.2013.143. ISSN 1754-2189. PMC 3969860. PMID 24157548.
  32. ^ Lavazza A, Massimini M (September 2018). "Cerebral organoids: ethical issues and consciousness assessment". Journal of Medical Ethics. 44 (9): 606–610. doi:10.1136/medethics-2017-104555. PMID 29491041.
  33. ^ Prosser Scully, Ruby (6 July 2019). "Miniature brains grown in the lab have human-like neural activity". New Scientist. No. 3237.
  34. ^ Sample, Ian (21 October 2019). "Scientists 'may have crossed ethical line' in growing human brains". The Guardian. p. 15.
  35. ^ Cai, H., Ao, Z., Tian, C. et al. Brain organoid reservoir computing for artificial intelligence. Nat Electron (2023). https://doi.org/10.1038/s41928-023-01069-w.
  36. ^ Smirnova L, Caffo BS, Gracias DH, Huang Q, Morales Pantoja IE, Tang B, Zack DJ, Berlinicke CA, Boyd JL, Harris TD, Johnson EC, Kagan BJ, Kahn J, Muotri AR, Paulhamus BL, Schwamborn JC, Plotkin J, Szalay AS, Vogelstein JT, Worley PF and Hartung T. Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish. Front Sci (2023) 1:1017235. https://doi.org/10.3389/fsci.2023.1017235.
  37. ^ Sato, Toshiro; Stange, Daniel E.; Ferrante, Marc; Vries, Robert G.J.; van Es, Johan H.; van den Brink, Stieneke; van Houdt, Winan J.; Pronk, Apollo; van Gorp, Joost; Siersema, Peter D.; Clevers, Hans (November 2011). "Long-term Expansion of Epithelial Organoids From Human Colon, Adenoma, Adenocarcinoma, and Barrett's Epithelium". Gastroenterology. 141 (5): 1762–1772. doi:10.1053/j.gastro.2011.07.050. ISSN 0016-5085. PMID 21889923.
  38. ^ Jung, Peter; Sato, Toshiro; Merlos-Suárez, Anna; Barriga, Francisco M; Iglesias, Mar; Rossell, David; Auer, Herbert; Gallardo, Mercedes; Blasco, Maria A; Sancho, Elena; Clevers, Hans (October 2011). "Isolation and in vitro expansion of human colonic stem cells". Nature Medicine. 17 (10): 1225–1227. doi:10.1038/nm.2470. ISSN 1078-8956. PMID 21892181. S2CID 205388154.
  39. ^ Cai T, Qi Y, Jergens A, Wannemuehler M, Barrett TA, Wang Q. Effects of six common dietary nutrients on murine intestinal organoid growth. PLoS One. 2018 Feb 1;13(2):e0191517. https://doi.org/10.1371/journal.pone.0191517. PMID: 29389993; PMCID: PMC5794098.
  40. ^ Qi Y, Lohman J, Bratlie KM, Peroutka-Bigus N, Bellaire B, Wannemuehler M, Yoon KJ, Barrett TA, Wang Q. Vitamin C and B3 as new biomaterials to alter intestinal stem cells. Journal of Biomedical Materials Research Part A. 2019 Sep;107(9):1886–1897. https://doi.org/10.1002/jbm.a.36715. Epub 2019 May 23. PMID: 31071241; PMCID: PMC6626554.
  41. ^ Davoudi Z, Peroutka-Bigus N, Bellaire B, Wannemuehler M, Barrett TA, Narasimhan B, Wang Q. Intestinal organoids containing poly(lactic-co-glycolic acid) nanoparticles for the treatment of inflammatory bowel diseases. Journal of Biomedical Materials Research Part A. 2018 Apr;106(4):876–886. https://doi.org/10.1002/jbm.a.36305. Epub 2017 Dec 21. PMID: 29226615; PMCID: PMC5826879.
  42. ^ Davoudi Z, Peroutka-Bigus N, Bellaire B, Jergens A, Wannemuehler M, Wang Q. Gut Organoid as a New Platform to Study Alginate and Chitosan Mediated PLGA Nanoparticles for Drug Delivery. Marine Drugs. 2021 May 20;19(5):282. https://doi.org/10.3390/md19050282. PMID: 34065505; PMCID: PMC8161322.
  43. ^ Qi Y, Shi E, Peroutka-Bigus N, Bellaire B, Wannemuehler M, Jergens A, Barrett T, Wu Y, Wang Q. Ex Vivo Study of Telluride Nanowires in Minigut. Journal of Biomedical Nanotechnology. 2018 May 1;14(5):978–986. https://doi.org/10.1166/jbn.2018.2578. PMID: 29883567
  44. ^ Reding B, Carter P, Qi Y, Li Z, Wu Y, Wannemuehler M, Bratlie KM, Wang Q. Manipulate intestinal organoids with niobium carbide nanosheets. Journal of Biomedical Materials Research Part A. 2021 Apr;109(4):479–487. https://doi.org/10.1002/jbm.a.37032. Epub 2020 Jun 17. PMID: 32506610.
  45. ^ Zietek T, Giesbertz P, Ewers M, Reichart F, Weinmüller M, Demir IE, et al. (2020). "Organoids to Study Intestinal Nutrient Transport, Drug Uptake and Metabolism – Update to the Human Model and Expansion of Applications". Frontiers in Bioengineering and Biotechnology. 8: 577656. doi:10.3389/fbioe.2020.577656. PMC 7516017. PMID 33015026.
  46. ^ Zietek T, Rath E, Haller D, Daniel H (November 2015). "Intestinal organoids for assessing nutrient transport, sensing and incretin secretion". Scientific Reports. 5 (1): 16831. Bibcode:2015NatSR...516831Z. doi:10.1038/srep16831. PMC 4652176. PMID 26582215.
  47. ^ Rahmani, Sara; Breyner, Natalia M.; Su, Hsuan-Ming; Verdu, Elena F.; Didar, Tohid F. (2019-02-01). "Intestinal organoids: A new paradigm for engineering intestinal epithelium in vitro". Biomaterials. 194: 195–214. doi:10.1016/j.biomaterials.2018.12.006. ISSN 0142-9612. PMID 30612006. S2CID 58603850.
  48. ^ Sun L, Rollins D, Qi Y, Fredericks J, Mansell TJ, Jergens A, Phillips GJ, Wannemuehler M, Wang Q. TNFα regulates intestinal organoids from mice with both defined and conventional microbiota. International Journal of Biological Macromolecules. 2020 Dec 1;164:548–556. https://doi.org/10.1016/j.ijbiomac.2020.07.176. Epub 2020 Jul 18. PMID: 32693143; PMCID: PMC7657954.
  49. ^ Tong T, Qi Y, Rollins D, Bussiere LD, Dhar D, Miller CL, Yu C, Wang Q. Rational design of oral drugs targeting mucosa delivery with gut organoid platforms. Bioactive Materials. 2023; 30: 116–128. https://doi.org/10.1016/j.bioactmat.2023.07.014. PMID: 37560199.
  50. ^ Davoudi Z, Atherly T, Borcherding DC, Jergens AE, Wannemuehler M, Barrett TA, Wang Q. Study Transportation of Drugs within Newly Established Murine Colon Organoid Systems. Advanced Biology. 2023; e2300103. https://doi.org/10.1002/adbi.202300103. PMID: 37607116.
  51. ^ Lindemans C, Mertelsmann A, Dudakov JA, Velardi E, Hua G, O'Connor M, et al. (2014). "IL-22 Administration Protects Intestinal Stem Cells from Gvhd". Biology of Blood and Marrow Transplantation. 20 (2): S53–S54. doi:10.1016/j.bbmt.2013.12.056.
  52. ^ Zhang, Yong-Guo; Wu, Shaoping; Xia, Yinglin; Sun, Jun (September 2014). "Salmonella -infected crypt-derived intestinal organoid culture system for host-bacterial interactions". Physiological Reports. 2 (9): e12147. doi:10.14814/phy2.12147. PMC 4270227. PMID 25214524.
  53. ^ Geiser, Petra; Di Martino, Maria Letizia; Samperio Ventayol, Pilar; Eriksson, Jens; Sima, Eduardo; Al-Saffar, Anas Kh.; Ahl, David; Phillipson, Mia; Webb, Dominic-Luc; Sundbom, Magnus; Hellström, Per M. (2021-02-23). Sperandio, Vanessa (ed.). "Salmonella enterica Serovar Typhimurium Exploits Cycling through Epithelial Cells To Colonize Human and Murine Enteroids". mBio. 12 (1). doi:10.1128/mBio.02684-20. ISSN 2161-2129. PMC 7844539. PMID 33436434.
  54. ^ Dutta, Devanjali; Heo, Inha; O'Connor, Roberta (2019-09-14). "Studying Cryptosporidium Infection in 3D Tissue-derived Human Organoid Culture Systems by Microinjection". Journal of Visualized Experiments (151): 59610. doi:10.3791/59610. ISSN 1940-087X. PMID 31566619. S2CID 203377662.
  55. ^ Co, Julia Y.; Margalef-Català, Mar; Li, Xingnan; Mah, Amanda T.; Kuo, Calvin J.; Monack, Denise M.; Amieva, Manuel R. (February 2019). "Controlling Epithelial Polarity: A Human Enteroid Model for Host-Pathogen Interactions". Cell Reports. 26 (9): 2509–2520.e4. doi:10.1016/j.celrep.2019.01.108. PMC 6391775. PMID 30811997.
  56. ^ Tong T , Qi Y , Bussiere LD , Wannemuehler M , Miller CL , Wang Q , Yu C . Transport of artificial virus-like nanocarriers through intestinal monolayers via microfold cells. Nanoscale. 2020 Aug 14;12(30):16339-16347. https://doi.org/10.1039/D0NR03680C. Epub 2020 Jul 29. PMID: 32725029.
  57. ^ a b Noel, Gaelle; Baetz, Nicholas W.; Staab, Janet F.; Donowitz, Mark; Kovbasnjuk, Olga; Pasetti, Marcela F.; Zachos, Nicholas C. (2017-05-31). "A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions". Scientific Reports. 7 (1): 45270. Bibcode:2017NatSR...745270N. doi:10.1038/srep45270. ISSN 2045-2322. PMC 5366908. PMID 28345602.
  58. ^ Bouchi R, Foo KS, Hua H, Tsuchiya K, Ohmura Y, Sandoval PR, Ratner LE, Egli D, Leibel RL, Accili D (June 2014). "FOXO1 inhibition yields functional insulin-producing cells in human gut organoid cultures". Nature Communications. 5: 4242. Bibcode:2014NatCo...5.4242B. doi:10.1038/ncomms5242. PMC 4083475. PMID 24979718.
  59. ^ Sontheimer-Phelps, Alexandra; Chou, David B.; Tovaglieri, Alessio; Ferrante, Thomas C.; Duckworth, Taylor; Fadel, Cicely; Frismantas, Viktoras; Sutherland, Arlene D.; Jalili-Firoozinezhad, Sasan; Kasendra, Magdalena; Stas, Eric (2020). "Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology". Cellular and Molecular Gastroenterology and Hepatology. 9 (3): 507–526. doi:10.1016/j.jcmgh.2019.11.008. PMC 7036549. PMID 31778828.
  60. ^ Grassart, Alexandre; Malardé, Valérie; Gobaa, Samy; Sartori-Rupp, Anna; Kerns, Jordan; Karalis, Katia; Marteyn, Benoit; Sansonetti, Philippe; Sauvonnet, Nathalie (September 2019). "Bioengineered Human Organ-on-Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection". Cell Host & Microbe. 26 (3): 435–444.e4. doi:10.1016/j.chom.2019.08.007. PMID 31492657. S2CID 201868491.
  61. ^ a b c McCracken KW, Catá EM, Crawford CM, Sinagoga KL, Schumacher M, Rockich BE, et al. (December 2014). "Modelling human development and disease in pluripotent stem-cell-derived gastric organoids". Nature. 516 (7531): 400–4. Bibcode:2014Natur.516..400M. doi:10.1038/nature13863. PMC 4270898. PMID 25363776.
  62. ^ Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH, et al. (January 2010). "Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro". Cell Stem Cell. 6 (1): 25–36. doi:10.1016/j.stem.2009.11.013. PMID 20085740.
  63. ^ Li X, Nadauld L, Ootani A, Corney DC, Pai RK, Gevaert O, et al. (July 2014). "Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture". Nature Medicine. 20 (7): 769–77. doi:10.1038/nm.3585. PMC 4087144. PMID 24859528.
  64. ^ a b Nadauld LD, Garcia S, Natsoulis G, Bell JM, Miotke L, Hopmans ES, et al. (August 2014). "Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer". Genome Biology. 15 (8): 428. doi:10.1186/s13059-014-0428-9. PMC 4145231. PMID 25315765.
  65. ^ a b Hisha H, Tanaka T, Kanno S, Tokuyama Y, Komai Y, Ohe S, et al. (November 2013). "Establishment of a novel lingual organoid culture system: generation of organoids having mature keratinized epithelium from adult epithelial stem cells". Scientific Reports. 3: 3224. Bibcode:2013NatSR...3E3224H. doi:10.1038/srep03224. PMC 3828633. PMID 24232854.
  66. ^ a b Aihara E, Mahe MM, Schumacher MA, Matthis AL, Feng R, Ren W, et al. (November 2015). "Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid". Scientific Reports. 5: 17185. Bibcode:2015NatSR...517185A. doi:10.1038/srep17185. PMC 4665766. PMID 26597788.
  67. ^ Ren W, Lewandowski BC, Watson J, Aihara E, Iwatsuki K, Bachmanov AA, Margolskee RF, Jiang P (November 2014). "Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo". Proceedings of the National Academy of Sciences of the United States of America. 111 (46): 16401–6. Bibcode:2014PNAS..11116401R. doi:10.1073/pnas.1409064111. PMC 4246268. PMID 25368147.
  68. ^ Hermans, F; Hasevoets, S; Vankelecom, H; Bronckaers, A; Lambrichts, I (18 March 2024). "From Pluripotent Stem Cells to Organoids and Bioprinting: Recent Advances in Dental Epithelium and Ameloblast Models to Study Tooth Biology and Regeneration". Stem Cell Reviews and Reports. doi:10.1007/s12015-024-10702-w. PMID 38498295.
  69. ^ Martin A, Barbesino G, Davies TF (1999). "T-cell receptors and autoimmune thyroid disease—signposts for T-cell-antigen driven diseases". International Reviews of Immunology. 18 (1–2): 111–40. doi:10.3109/08830189909043021. PMID 10614741.
  70. ^ Bredenkamp N, Ulyanchenko S, O'Neill KE, Manley NR, Vaidya HJ, Blackburn CC (September 2014). "An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts". Nature Cell Biology. 16 (9): 902–8. doi:10.1038/ncb3023. PMC 4153409. PMID 25150981.
  71. ^ a b c Vianello F, Poznansky MC (2007). "Generation of a tissue-engineered thymic organoid". Immunological Tolerance. Methods in Molecular Biology. Vol. 380. pp. 163–70. doi:10.1007/978-1-59745-395-0_9. ISBN 978-1-59745-395-0. PMID 17876092.
  72. ^ Sakib, Sadman; et al. (1 June 2019). "Formation of organotypic testicular organoids in microwell culture". Biology of Reproduction. 100 (6): 1648–1660. doi:10.1093/biolre/ioz053. PMC 7302515. PMID 30927418.
  73. ^ Drost, Jarno; Karthaus, Wouter R.; Gao, Dong; Driehuis, Else; Sawyers, Charles L.; Chen, Yu; Clevers, Hans (21 January 2016). "Organoid culture systems for prostate epithelial and cancer tissue". Nature Protocols. 11 (2): 347–358. doi:10.1038/nprot.2016.006. ISSN 1750-2799. PMC 4793718. PMID 26797458.
  74. ^ Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen MM, et al. (January 2015). "Long-term culture of genome-stable bipotent stem cells from adult human liver". Cell. 160 (1–2): 299–312. doi:10.1016/j.cell.2014.11.050. PMC 4313365. PMID 25533785.
  75. ^ Li P, Li Y, Wang Y, Liu J, Lavrijsen M, Li Y, Zhang R, Verstegen MMA, Wang Y, Li TC, Ma Z, Kainov DE, Bruno MJ, de Man RA, van der Laan LJW, Peppelenbosch MP, Pan Q (2022). "Recapitulating hepatitis E virus-host interactions and facilitating antiviral drug discovery in human liver-derived organoids". Science Advances. 8 (3): 103–111. Bibcode:2022SciA....8.5908L. doi:10.1126/sciadv.abj5908. hdl:11250/3047921. PMID 5044825. S2CID 246069868.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  76. ^ Huch M, Bonfanti P, Boj SF, Sato T, Loomans CJ, van de Wetering M, et al. (October 2013). "Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis". The EMBO Journal. 32 (20): 2708–21. doi:10.1038/emboj.2013.204. PMC 3801438. PMID 24045232.
  77. ^ Hou S, Tiriac H, Sridharan BP, Scampavia L, Madoux F, Seldin J; et al. (2018). "Advanced Development of Primary Pancreatic Organoid Tumor Models for High-Throughput Phenotypic Drug Screening". SLAS Discov. 23 (6): 574–584. doi:10.1177/2472555218766842. PMC 6013403. PMID 29673279.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  78. ^ Wolff RA, Wang-Gillam A, Alvarez H, Tiriac H, Engle D, Hou S; et al. (2018). "Dynamic changes during the treatment of pancreatic cancer". Oncotarget. 9 (19): 14764–14790. doi:10.18632/oncotarget.24483. PMC 5871077. PMID 29599906.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  79. ^ Below, Christopher R.; Kelly, Joanna; Brown, Alexander; Humphries, Jonathan D.; Hutton, Colin; Xu, Jingshu; Lee, Brian Y.; Cintas, Celia; Zhang, Xiaohong; Hernandez-Gordillo, Victor; Stockdale, Linda (2021-09-13). "A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids". Nature Materials. 21 (1): 110–119. doi:10.1038/s41563-021-01085-1. ISSN 1476-4660. PMC 7612137. PMID 34518665.
  80. ^ Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. (October 2007). "Identification of stem cells in small intestine and colon by marker gene Lgr5". Nature. 449 (7165): 1003–7. Bibcode:2007Natur.449.1003B. doi:10.1038/nature06196. PMID 17934449. S2CID 4349637.
  81. ^ Lee JH, Bhang DH, Beede A, Huang TL, Stripp BR, Bloch KD, et al. (January 2014). "Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis". Cell. 156 (3): 440–55. doi:10.1016/j.cell.2013.12.039. PMC 3951122. PMID 24485453.
  82. ^ Takasato M, Er PX, Chiu HS, Maier B, Baillie GJ, Ferguson C, et al. (October 2015). "Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis". Nature. 526 (7574): 564–8. Bibcode:2015Natur.526..564T. doi:10.1038/nature15695. PMID 26444236. S2CID 4443766.
  83. ^ a b c Freedman BS, Brooks CR, Lam AQ, Fu H, Morizane R, Agrawal V, et al. (October 2015). "Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids". Nature Communications. 6: 8715. Bibcode:2015NatCo...6.8715F. doi:10.1038/ncomms9715. PMC 4620584. PMID 26493500.
  84. ^ Morizane R, Lam AQ, Freedman BS, Kishi S, Valerius MT, Bonventre JV (November 2015). "Nephron organoids derived from human pluripotent stem cells model kidney development and injury". Nature Biotechnology. 33 (11): 1193–200. doi:10.1038/nbt.3392. PMC 4747858. PMID 26458176.
  85. ^ van den Brink SC, Baillie-Johnson P, Balayo T, Hadjantonakis AK, Nowotschin S, Turner DA, et al. (November 2014). "Symmetry breaking, germ layer specification and axial organisation in aggregates of mouse embryonic stem cells". Development. 141 (22): 4231–42. doi:10.1242/dev.113001. PMC 4302915. PMID 25371360.
  86. ^ Turner DA, Baillie-Johnson P, Martinez Arias A (February 2016). "Organoids and the genetically encoded self-assembly of embryonic stem cells". BioEssays. 38 (2): 181–91. doi:10.1002/bies.201500111. PMC 4737349. PMID 26666846.
  87. ^ Turner DA, Girgin M, Alonso-Crisostomo L, Trivedi V, Baillie-Johnson P, Glodowski CR, et al. (November 2017). "Anteroposterior polarity and elongation in the absence of extra-embryonic tissues and of spatially localised signalling in gastruloids: mammalian embryonic organoids". Development. 144 (21): 3894–3906. doi:10.1242/dev.150391. PMC 5702072. PMID 28951435.
  88. ^ a b Beccari L, Moris N, Girgin M, Turner DA, Baillie-Johnson P, Cossy AC, et al. (October 2018). "Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids". Nature. 562 (7726): 272–276. Bibcode:2018Natur.562..272B. doi:10.1038/s41586-018-0578-0. PMID 30283134. S2CID 52915553.
  89. ^ "Blastoid: The backstory of the formation of blastocyst-like structure solely from stem cells". 2018-06-27.
  90. ^ "Nicolas Rivron Lab | Blastoid | Netherlands".
  91. ^ Rivron NC, Frias-Aldeguer J, Vrij EJ, Boisset JC, Korving J, Vivié J, et al. (May 2018). "Blastocyst-like structures generated solely from stem cells" (PDF). Nature. 557 (7703): 106–111. Bibcode:2018Natur.557..106R. doi:10.1038/s41586-018-0051-0. PMID 29720634. S2CID 13749109.
  92. ^ Rawlings TM, Makwana K, Tryfonos M, Lucas ES (July 2021). "Organoids to model the endometrium: implantation and beyond". Reprod Fertil. 2 (3): R85–R101. doi:10.1530/RAF-21-0023. PMC 8801025. PMID 35118399.
  93. ^ Lee EJ, Kim DE, Azeloglu EU, Costa KD (February 2008). "Engineered cardiac organoid chambers: toward a functional biological model ventricle". Tissue Engineering. Part A. 14 (2): 215–25. doi:10.1089/tea.2007.0351. PMID 18333774.
  94. ^ Molteni M (2018-06-27). "These Beating Mini-Hearts Could Save Big Bucks—And Maybe Lives". WIRED. Retrieved 2018-06-30.
  95. ^ Wiley LA, Burnight ER, DeLuca AP, Anfinson KR, Cranston CM, Kaalberg EE, et al. (July 2016). "cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness". Scientific Reports. 6: 30742. Bibcode:2016NatSR...630742W. doi:10.1038/srep30742. PMC 4965859. PMID 27471043.
  96. ^ Zilova, Lucie; Weinhardt, Venera; Tavhelidse, Tinatini; Schlagheck, Christina; Thumberger, Thomas; Wittbrodt, Joachim (2021-07-12). Martínez Arias, Alfonso; Stainier, Didier YR; Martínez Arias, Alfonso (eds.). "Fish primary embryonic pluripotent cells assemble into retinal tissue mirroring in vivo early eye development". eLife. 10: e66998. doi:10.7554/eLife.66998. ISSN 2050-084X. PMC 8275126. PMID 34252023.
  97. ^ Sachs, Norman; de Ligt, Joep; Kopper, Oded; Gogola, Ewa; Bounova, Gergana; Weeber, Fleur; Balgobind, Anjali Vanita; Wind, Karin; Gracanin, Ana; Begthel, Harry; Korving, Jeroen; van Boxtel, Ruben; Duarte, Alexandra Alves; Lelieveld, Daphne; et al. (2018). "A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity". Cell. 172 (1–2): 373–386.e10. doi:10.1016/j.cell.2017.11.010. ISSN 0092-8674. PMID 29224780.
  98. ^ van de Wetering, Marc; Francies, Hayley; Francis, Joshua; Bounova, Gergana; Iorio, Francesco; Pronk, Apollo; van Houdt, Winan; van Gorp, Joost; Taylor-Weiner, Amaro; Kester, Lennart; McLaren-Douglas, Anne; Blokker, Joyce; Jaksani, Sridevi; Bartfeld, Sina; et al. (2015). "Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients". Cell. 161 (4): 933–945. doi:10.1016/j.cell.2015.03.053. ISSN 0092-8674. PMC 6428276. PMID 25957691.
  99. ^ Quereda V, Hou S, Madoux F, Scampavia L, Spicer TP, Duckett D (2018). "A Cytotoxic Three-Dimensional-Spheroid, High-Throughput Assay Using Patient-Derived Glioma Stem Cells". SLAS Discov. 23 (8): 842–849. doi:10.1177/2472555218775055. PMC 6102052. PMID 29750582.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  100. ^ Dayton, Talya L.; Alcala, Nicolas; Moonen, Laura; den Hartigh, Lisanne; Geurts, Veerle; Mangiante, Lise; Lap, Lisa; Dost, Antonella F.M.; Beumer, Joep; Levy, Sonja; van Leeuwaarde, Rachel S.; Hackeng, Wenzel M.; Samsom, Kris; Voegele, Catherine; et al. (2023). "Druggable growth dependencies and tumor evolution analysis in patient-derived organoids of neuroendocrine neoplasms from multiple body sites". Cancer Cell. 41 (12): 2083–2099. doi:10.1016/j.ccell.2023.11.007. ISSN 1535-6108. PMID 38086335.
  101. ^ Zidarič, Tanja; Gradišnik, Lidija; Velnar, Tomaž (2022-04-01). "Astrocytes and human artificial blood-brain barrier models". Bosnian Journal of Basic Medical Sciences. 22 (5): 651–672. doi:10.17305/bjbms.2021.6943. ISSN 1840-4812. PMC 9519155. PMID 35366791.
  102. ^ Zietek T, Rath E, Haller D, Daniel H (November 2015). "Intestinal organoids for assessing nutrient transport, sensing and incretin secretion". Scientific Reports. 5: 16831. Bibcode:2015NatSR...516831Z. doi:10.1038/srep16831. PMC 4652176. PMID 26582215.
  103. ^ a b c Cruz NM, Song X, Czerniecki SM, Gulieva RE, Churchill AJ, Kim YK, et al. (November 2017). "Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease". Nature Materials. 16 (11): 1112–1119. Bibcode:2017NatMa..16.1112C. doi:10.1038/nmat4994. PMC 5936694. PMID 28967916.
  104. ^ a b c Kim YK, Refaeli I, Brooks CR, Jing P, Gulieva RE, Hughes MR, et al. (December 2017). "Gene-Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development". Stem Cells. 35 (12): 2366–2378. doi:10.1002/stem.2707. PMC 5742857. PMID 28905451.
  105. ^ Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. (November 2007). "Induction of pluripotent stem cells from adult human fibroblasts by defined factors" (PDF). Cell. 131 (5): 861–72. doi:10.1016/j.cell.2007.11.019. hdl:2433/49782. PMID 18035408. S2CID 8531539.
  106. ^ a b c Hsieh WC, Ramadesikan S, Fekete D, Aguilar RC (2018-02-14). "Kidney-differentiated cells derived from Lowe Syndrome patient's iPSCs show ciliogenesis defects and Six2 retention at the Golgi complex". PLOS ONE. 13 (2): e0192635. Bibcode:2018PLoSO..1392635H. doi:10.1371/journal.pone.0192635. PMC 5812626. PMID 29444177.
  107. ^ Howden SE, Thomson JA, Little MH (May 2018). "Simultaneous reprogramming and gene editing of human fibroblasts". Nature Protocols. 13 (5): 875–898. doi:10.1038/nprot.2018.007. PMC 5997775. PMID 29622803.
  108. ^ a b c d Forbes TA, Howden SE, Lawlor K, Phipson B, Maksimovic J, Hale L, et al. (May 2018). "Patient-iPSC-Derived Kidney Organoids Show Functional Validation of a Ciliopathic Renal Phenotype and Reveal Underlying Pathogenetic Mechanisms". American Journal of Human Genetics. 102 (5): 816–831. doi:10.1016/j.ajhg.2018.03.014. PMC 5986969. PMID 29706353.
  109. ^ a b Tanigawa S, Islam M, Sharmin S, Naganuma H, Yoshimura Y, Haque F, et al. (September 2018). "Organoids from Nephrotic Disease-Derived iPSCs Identify Impaired NEPHRIN Localization and Slit Diaphragm Formation in Kidney Podocytes". Stem Cell Reports. 11 (3): 727–740. doi:10.1016/j.stemcr.2018.08.003. PMC 6135868. PMID 30174315.
  110. ^ Engle SJ, Blaha L, Kleiman RJ (November 2018). "Best Practices for Translational Disease Modeling Using Human iPSC-Derived Neurons". Neuron. 100 (4): 783–797. doi:10.1016/j.neuron.2018.10.033. PMID 30465765.
  111. ^ "Metabolites". www.mdpi.com. Retrieved 2022-10-16.
  112. ^ a b Dekkers JF, Wiegerinck CL, de Jonge HR, Bronsveld I, Janssens HM, de Winter-de Groot KM, et al. (July 2013). "A functional CFTR assay using primary cystic fibrosis intestinal organoids". Nature Medicine. 19 (7): 939–45. doi:10.1038/nm.3201. PMID 23727931. S2CID 5369669.
  113. ^ a b Dekkers JF, Berkers G, Kruisselbrink E, Vonk A, de Jonge HR, Janssens HM, et al. (June 2016). "Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis". Science Translational Medicine. 8 (344): 344ra84. doi:10.1126/scitranslmed.aad8278. PMID 27334259. S2CID 19462535.
  114. ^ Schwank G, Koo BK, Sasselli V, Dekkers JF, Heo I, Demircan T, et al. (December 2013). "Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients". Cell Stem Cell. 13 (6): 653–8. doi:10.1016/j.stem.2013.11.002. PMID 24315439.
  115. ^ "World's first mini organ transportation to a patient with ulcerative colitis". Tokyo Medical and Dental University via medicalxpress.com. Retrieved 18 September 2022.
  116. ^ Watanabe, Satoshi; Kobayashi, Sakurako; Ogasawara, Nobuhiko; Okamoto, Ryuichi; Nakamura, Tetsuya; Watanabe, Mamoru; Jensen, Kim B.; Yui, Shiro (March 2022). "Transplantation of intestinal organoids into a mouse model of colitis". Nature Protocols. 17 (3): 649–671. doi:10.1038/s41596-021-00658-3. ISSN 1750-2799. PMID 35110738. S2CID 246488596.
  117. ^ a b c d e Ader M, Tanaka EM (December 2014). "Modeling human development in 3D culture". Current Opinion in Cell Biology. 31: 23–8. doi:10.1016/j.ceb.2014.06.013. PMID 25033469.
  118. ^ Martinez-Morales JR, Cavodeassi F, Bovolenta P (2017). "Coordinated Morphogenetic Mechanisms Shape the Vertebrate Eye". Frontiers in Neuroscience. 11: 721. doi:10.3389/fnins.2017.00721. PMC 5742352. PMID 29326547.
  119. ^ Gordon, Aaron; Yoon, Se-Jin; Tran, Stephen S.; Makinson, Christopher D.; Park, Jin Young; Andersen, Jimena; Valencia, Alfredo M.; Horvath, Steve; Xiao, Xinshu; Huguenard, John R.; Pașca, Sergiu P. (2021-02-22). "Long-term maturation of human cortical organoids matches key early postnatal transitions". Nature Neuroscience. 24 (3): 331–342. doi:10.1038/s41593-021-00802-y. ISSN 1546-1726. PMC 8109149. PMID 33619405.

Further reading edit

  • Willyard C (July 2015). "The boom in mini stomachs, brains, breasts, kidneys and more". Nature. 523 (7562): 520–2. Bibcode:2015Natur.523..520W. doi:10.1038/523520a. PMID 26223610.
  • Kelly Rae Chi (2015). Orchestrating Organoids. A guide to crafting tissues in a dish that reprise in vivo organs. The Scientist.
  • Takebe T, Enomura M, Yoshizawa E, Kimura M, Koike H, Ueno Y, Matsuzaki T, Yamazaki T, Toyohara T, Osafune K, Nakauchi H, Yoshikawa HY, Taniguchi H (May 2015). "Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell-Driven Condensation". Cell Stem Cell. 16 (5): 556–65. doi:10.1016/j.stem.2015.03.004. PMID 25891906.
  • Turner DA, Baillie-Johnson P, Martinez Arias A (February 2016). "Organoids and the genetically encoded self-assembly of embryonic stem cells". BioEssays. 38 (2): 181–91. doi:10.1002/bies.201500111. PMC 4737349. PMID 26666846.
  • Organoid-based regenerative medicine

April 14, 2024
organoid, appearing, anime, series, zoids, organoid, miniaturised, simplified, version, organ, produced, vitro, three, dimensions, that, mimics, functional, structural, biological, complexity, that, organ, they, derived, from, cells, from, tissue, embryonic, s. For Organoids appearing in an anime series see Zoids Organoids An organoid is a miniaturised and simplified version of an organ produced in vitro in three dimensions that mimics the key functional structural and biological complexity of that organ 1 They are derived from one or a few cells from a tissue embryonic stem cells or induced pluripotent stem cells which can self organize in three dimensional culture owing to their self renewal and differentiation capacities The technique for growing organoids has rapidly improved since the early 2010s and The Scientist names it as one of the biggest scientific advancements of 2013 2 Scientists and engineers use organoids to study development and disease in the laboratory drug discovery and development in industry 3 personalized diagnostics and medicine gene and cell therapies tissue engineering and regenerative medicine Intestinal organoid grown from Lgr5 stem cells Contents 1 History 2 Properties 3 Process 4 Types 4 1 Cerebral organoid 4 2 Gastrointestinal organoid 4 2 1 Intestinal organoid 4 2 2 Gastric organoid 4 3 Lingual organoid 4 4 Other 5 Basic research 6 Models of disease 7 Personalised medicine 8 Organoid transplants 9 As a model for developmental biology 10 See also 11 References 12 Further readingHistory editAttempts to create organs in vitro started with one of the first dissociation reaggregation experiments 4 where Henry Van Peters Wilson demonstrated that mechanically dissociated sponge cells can reaggregate and self organize to generate a whole organism 5 In the subsequent decades multiple labs were able to generate different types of organs 4 in vitro through the dissociation and reaggregation of organ tissues obtained from amphibians 6 and embryonic chicks 7 The formation of first tissue like colonies in vitro was observed for the first time by co culturing keratinocytes and 3T3 fibroblasts 8 The phenomena of mechanically dissociated cells aggregating and reorganizing to reform the tissue they were obtained from subsequently led to the development of the differential adhesion hypothesis by Malcolm Steinberg 4 With the advent of the field of stem cell biology the potential of stem cells to form organs in vitro was realized early on with the observation that when stem cells form teratomas or embryoid bodies the differentiated cells can organize into different structures resembling those found in multiple tissue types 4 The advent of the field of organoids started with a shift from culturing and differentiating stem cells in two dimensional 2D media to three dimensional 3D media to allow for the development of the complex 3 dimensional structures of organs 4 Utilization of 3D media culture media methods for the structural organization was made possible with the development of extracellular matrices ECM 9 In the late 1980s Bissell and colleagues showed that a laminin rich gel can be used as a basement membrane for differentiation and morphogenesis in cell cultures of mammary epithelial cells 10 11 Since 1987 researchers have devised different methods for 3D culturing and were able to utilize different types of stem cells to generate organoids resembling a multitude of organs 4 In the 1990s in addition to their role in physical support the role of ECM components in gene expression by their interaction with integrin based focal adhesion pathways was reported 12 In 2006 Yaakov Nahmias and David Odde showed the self assembly of vascular liver organoid maintained for over 50 days in vitro 13 In 2008 Yoshiki Sasai and his team at RIKEN institute demonstrated that stem cells can be coaxed into balls of neural cells that self organize into distinctive layers 14 In 2009 the Laboratory of Hans Clevers at Hubrecht Institute and University Medical Center Utrecht Netherlands showed that single LGR5 expressing intestinal stem cells self organize to crypt villus structures in vitro without necessity of a mesenchymal niche making them the first organoids 15 In 2010 Mathieu Unbekandt amp Jamie A Davies demonstrated the production of renal organoids from murine fetus derived renogenic stem cells 16 In 2014 Qun Wang and co workers engineered collagen I and laminin based gels and synthetic foam biomaterials for the culture and delivery of intestinal organoids 17 and encapsulated DNA functionalized gold nanoparticles into intestinal organoids to form an intestinal Trojan horse for drug delivery and gene therapy 18 Subsequent reports showed significant physiological function of these organoids in vitro 19 and in vivo 20 21 Other significant early advancements included in 2013 Madeline Lancaster at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences established a protocol starting from pluripotent stem cells to generate cerebral organoids that mimic the developing human brain s cellular organization 22 Meritxell Huch and Craig Dorrell at Hubrecht Institute and University Medical Center Utrecht demonstrated that single Lgr5 cells from damaged mouse liver can be clonally expanded as liver organoids in Rspo1 based culture medium over several months 23 In 2014 Artem Shkumatov et al at the University of Illinois at Urbana Champaign demonstrated that cardiovascular organoids can be formed from ES cells through modulation of the substrate stiffness to which they adhere Physiological stiffness promoted three dimensionality of EBs and cardiomyogenic differentiation 24 In 2015 Takebe et al demonstrated a generalized method for organ bud formation from diverse tissues by combining pluripotent stem cell derived tissue specific progenitors or relevant tissue samples with endothelial cells and mesenchymal stem cells They suggested that the less mature tissues or organ buds generated through the self organized condensation principle might be the most efficient approach toward the reconstitution of mature organ functions after transplantation rather than condensates generated from cells of a more advanced stage 25 Properties editLancaster and Knoblich 4 define an organoid as a collection of organ specific cell types that develops from stem cells or organ progenitors self organizes through cell sorting and spatially restricted lineage commitment in a manner similar to in vivo and exhibits the following properties it has multiple organ specific cell types it is capable of recapitulating some specific function of the organ e g contraction neural activity endocrine secretion filtration excretion its cells are grouped together and spatially organized similar to an organ Process editOrganoid formation generally requires culturing the stem cells or progenitor cells in a 3D medium 4 Stem cells have the ability to self renew and differentiate into various cell subtypes and they enable understanding the processes of development and disease progression 26 Therefore organoids derived from stem cells enable studying biology and physiology at the organ level 27 The 3D medium can be made using an extracellular matrix hydrogel such as Matrigel or Cultrex BME which is a laminin rich extracellular matrix that is secreted by the Engelbreth Holm Swarm tumor line 28 Organoid bodies can then be made through embedding stem cells in the 3D medium 4 When pluripotent stem cells are used for the creation of the organoid the cells are usually but not all the time allowed to form embryoid bodies 4 Those embryoid bodies are then pharmacologically treated with patterning factors to drive the formation of the desired organoid identity 4 Organoids have also been created using adult stem cells extracted from the target organ and cultured in 3D media 29 Biochemical cues have been incorporated in 3D organoid cultures and with exposure of morphogenes morphogen inhibitors or growth factors organoid models can be developed using embryonic stem cells ESCs or adult stem cells ASCs Vascularization techniques can be utilized to embody microenvironments that are close to their counterparts physiologically Vasculature systems that can facilitate oxygen or nutrients to the inner mass of organoids can be achieved through microfluidic systems vascular endothelial growth factor delivery systems and endothelial cell coated modules 9 With patient derived induced pluripotent stem cells iPSCs 30 and CRISPR Cas based genome editing 31 technologies genome edited or mutated pluripotent stem cells PSCs with altered signaling cues can be generated to control intrinsic cues within organoids Types editA multitude of organ structures have been recapitulated using organoids 4 This section aims to outline the state of the field as of now through providing an abridged list of the organoids that have been successfully created along with a brief outline based on the most recent literature for each organoid and examples of how it has been utilized in research Cerebral organoid edit A cerebral organoid describes artificially grown in vitro miniature organs resembling the brain Cerebral organoids are created by culturing human pluripotent stem cells in a three dimensional structure using rotational bioreactor and develop over the course of months 22 The procedure has potential applications in the study of brain development physiology and function Cerebral organoids may experience simple sensations in response to external stimulation and neuroscientists are among those expressing concern that such organs could develop sentience They propose that further evolution of the technique needs to be subject to a rigorous oversight procedure 32 33 34 In 2023 researchers have built a hybrid biocomputer that combines a laboratory grown human brain organoids with conventional circuits and can complete tasks such as voice recognition 35 Cerebral Organoids are currently being used to research and develop Organoid Intelligence OI technologies 36 Gastrointestinal organoid edit Gastrointestinal organoids refer to organoids that recapitulate structures of the gastrointestinal tract The gastrointestinal tract arises from the endoderm which during development forms a tube that can be divided in three distinct regions which give rise to along with other organs the following sections of the gastrointestinal tract 4 The foregut gives rise to the oral cavity and the stomach The midgut gives rise to the small intestines and the ascending colon The hindgut gives rise to the rectum and the rest of the colonOrganoids have been created for the following structures of the gastrointestinal tract Intestinal organoid edit Intestinal organoids 15 have thus far been among the gut organoids generated directly from intestinal tissues or pluripotent stem cells 4 One way human pluripotent stem cells can be driven to form intestinal organoids is through first the application of activin A to drive the cells into a mesoendodermal identity followed by the pharmacological upregulation of Wnt3a and Fgf4 signaling pathways as they have been demonstrated to promote posterior gut fate 4 Intestinal organoids have also been generated from intestinal stem cells extracted from adult tissue and cultured in 3D media 29 These adult stem cell derived organoids are often referred to as enteroids or colonoids depending on their segment of origin and have been established from both the human and murine intestine 15 37 38 Intestinal organoids consist of a single layer of polarized intestinal epithelial cells surrounding a central lumen As such recapitulate the crypt villus structure of the intestine by recapitulating its function physiology and organization and maintaining all the cell types found normally in the structure including intestinal stem cells 4 Thus intestinal organoids are a valuable model to study intestinal nutrient transport 39 40 drug absorption and delivery 41 42 nanomaterials and nanomedicine 43 44 incretin hormone secretion 45 46 and infection by various enteropathogens 47 48 For example Qun Wang s team rationally designed artificial virus nanoparticles as oral drug delivery vehicles ODDVs with gut organoid derived mucosal models 49 and demonstrated a new concept of using newly established colon organoids as tools for high throughput drug screening toxicity testing and oral drug development 50 Intestinal organoids also recapitulate the crypt Villus structure to such a high degree of fidelity that they have been successfully transplanted to mouse intestines and are hence highly regarded as a valuable model for research 4 One of the fields of research that intestinal organoids have been utilized is that of stem cell niche Intestinal organoids were used to study the nature of the intestinal stem cell niche and research done with them demonstrated the positive role IL 22 has in maintaining in intestinal stem cells 51 along with demonstrating the roles of other cell types like neurons and fibroblasts in maintenance of intestinal stem cells 29 In the field of infection biology different intestinal organoid based model systems have been explored On one hand organoids can be infected in bulk by simply mixing them with the enteropathogen of interest 52 However to model infection via a more natural route starting from the intestinal lumen microinjection of the pathogen is required 53 54 In addition the polarity of intestinal organoids can be inverted 55 and they can even be dissociated into single cells and cultured as 2D monolayers 56 57 in order to make both the apical and basolateral sides of the epithelium more easily accessible Intestinal organoids have also demonstrated therapeutic potential 58 nbsp An intestinal organoid Minigut grows up in 7 days The scale bars are 200 mm In order to more accurately recapitulate the intestine in vivo co cultures of intestinal organoids and immune cells have been developed 57 Furthermore organ on a chip models combine intestinal organoids with other cell types such as endothelial or immune cells as well as peristaltic flow 59 60 Gastric organoid edit Gastric organoids recapitulate at least partly the physiology of the stomach Gastric organoids have been generated directly from pluripotent stem cells through the temporal manipulation of the FGF WNT BMP retinoic acid and EGF signalling pathways in three dimensional culture conditions 61 Gastric organoids have also been generated using LGR5 expressing stomach adult stem cells 62 Gastric organoids have been used as model for the study of cancer 63 64 along with human disease 61 and development 61 For example one study 64 investigated the underlying genetic alterations behind a patient s metastatic tumor population and identified that unlike the patient s primary tumor the metastasis had both alleles of the TGFBR2 gene mutated To further assess the role of TGFBR2 in the metastasis the investigators created organoids where TGFBR2 expression is knocked down through which they were able to demonstrate that reduced TGFBR2 activity leads to invasion and metastasis of cancerous tumors both in vitro and in vivo Lingual organoid edit Lingual organoids are organoids that recapitulate at least partly aspects of the tongue physiology Epithelial lingual organoids have been generated using BMI1 expressing epithelial stem cells in three dimensional culture conditions through the manipulation of EGF WNT and TGF b 65 This organoid culture however lacks taste receptors as these cells do not arise from Bmi1 expressing epithelial stem cells 65 Lingual taste bud organoids containing taste cells however have been created using the LGR5 or CD44 stem progenitor cells of circumvallate CV papilla tissue 66 These taste bud organoids have been successfully created both directly from isolated Lgr5 or LGR6 expressing taste stem progenitor cells 67 and indirectly through the isolation digestion and subsequent culturing of CV tissue containing Lgr5 or CD44 stem progenitor cells 66 Other edit Tooth organoid TO 68 see also tooth regeneration Thyroid organoid 69 Thymic organoid 70 Thymic organoids recapitulate at least partly the architecture and stem cell niche functionality of the thymus 71 which is a lymphoid organ where T cells mature Thymic organoids have been generated through the seeding of thymic stromal cells in 3 dimensional culture 71 Thymic organoids seem to successfully recapitulate the thymus function as co culturing human hematopoietic or bone marrow stem cells with mouse thymic organoids resulted in the production of T cells 71 dd Testicular organoid 72 Prostate organoid 73 Hepatic organoid 74 A recent study showed the usefulness of the technology for identifying novel medication for the treatment of hepatitis E as it allows to allows to recapitulate the entire viral life cycle 75 Pancreatic organoid 76 77 78 79 Recent advances in cell repellent microtiter plates has allowed rapid cost effective screening of large small molecule drug like libraries against 3D models of pancreas cancer These models are consistent in phenotype and expression profiles with those found in the lab of Dr David Tuveson dd Epithelial organoid 15 80 Lung organoid 81 Kidney organoid 16 82 83 84 Gastruloid embryonic organoid 85 86 87 88 Generates all embryonic axes and fully implements the collinear Hox gene expression patterns along the anteroposterior axis 88 Blastoid blastocyst like organoid 89 90 91 Endometrial organoid 92 Cardiac organoid 93 In 2018 hollow cardiac organoids were made to beat and to respond to stimuli to beat faster or slower 94 Retinal organoid 95 96 Breast cancer organoid 97 Colorectal cancer organoid 98 Glioblastoma organoid 99 3D organoid models of brain cancer derived from either patient derived explants PDX or direct from cancer tissue is now easily achievable and affords high throughput screening of these tumors against the current panel of approved drugs form around the world Neuroendocrine tumor organoid 100 Myelinoid Myelin organoid Blood brain barrier BBB organoid 101 Self assembled cell aggregates consisting of BMECs astrocytes and pericytes are emerging as a potential alternative to transwell and microfluidic models for certain applications These organoides can generate many features of the BBB such as the expression of tight junctions molecular transporters and drug efflux pumps and can therefore be used to model drug transport across the BBB Also they can serve as a model for evaluating the interactions between the BBB and adjacent brain tissue and provide a platform for understanding the combined abilities of a new drug to overcome the BBB and its effect on brain tissue In addition such models are highly scalable and easier to manufacture and operate than microfluidic devices However they have limited ability to reconstruct the morphology and physiology of the BBB and are unable to simulate physiological flow and shear stress Basic research editOrganoids enable to study how cells interact together in an organ their interaction with their environment how diseases affect them and the effect of drugs In vitro culture makes this system easy to manipulate and facilitates their monitoring While organs are difficult to culture because their size limits the penetration of nutrients the small size of organoids limits this problem On the other hand they do not exhibit all organ features and interactions with other organs are not recapitulated in vitro While research on stem cells and regulation of stemness was the first field of application of intestinal organoids 15 they are now also used to study e g uptake of nutrients drug transport and secretion of incretin hormones 102 This is of great relevance in the context of malabsorption diseases as well as metabolic diseases such as obesity insulin resistance and diabetes Models of disease editOrganoids provide an opportunity to create cellular models of human disease which can be studied in the laboratory to better understand the causes of disease and identify possible treatments The power of organoids in this regard was first shown for a genetic form of microcephaly where patient cells were used to make cerebral organoids which were smaller and showed abnormalities in early generation of neurons 22 In another example the genome editing system called CRISPR was applied to human pluripotent stem cells to introduce targeted mutations in genes relevant to two different kidney diseases polycystic kidney disease and focal segmental glomerulosclerosis 83 These CRISPR modified pluripotent stem cells were subsequently grown into human kidney organoids which exhibited disease specific phenotypes Kidney organoids from stem cells with polycystic kidney disease mutations formed large translucent cyst structures from kidney tubules When cultured in the absence of adherent cues in suspension these cysts reached sizes of 1 cm in diameter over several months 103 Kidney organoids with mutations in a gene linked to focal segmental glomerulosclerosis developed junctional defects between podocytes the filtering cells affected in that disease 104 Importantly these disease phenotypes were absent in control organoids of identical genetic background but lacking the CRISPR mutations 83 103 104 Comparison of these organoid phenotypes to diseased tissues from mice and humans suggested similarities to defects in early development 103 104 As first developed by Takahashi and Yamanaka in 2007 induced pluripotent stem cells iPSC can also be reprogrammed from patient skin fibroblasts 105 These stem cells carry the exact genetic background of the patient including any genetic mutations which might contribute to the development of human disease Differentiation of these cells into kidney organoids has been performed from patients with Lowe Syndrome due to ORCL1 mutations 106 This report compared kidney organoids differentiated from patient iPSC to unrelated control iPSC and demonstrated an inability of patient kidney cells to mobilise transcription factor SIX2 from the golgi complex 106 Because SIX2 is a well characterised marker of nephron progenitor cells in the cap mesenchyme the authors concluded that renal disease frequently seen in Lowe Syndrome global failure of proximal tubule reabsorption or renal Fanconi syndrome could be related to alteration in nephron patterning arising from nephron progenitor cells lacking this important SIX2 gene expression 106 Other studies have used CRISPR gene editing to correct the patient s mutation in the patient iPSC cells to create an isogenic control which can be performed simultaneously with iPSC reprogramming 107 108 109 Comparison of a patient iPSC derived organoid against an isogenic control is the current gold standard in the field as it permits isolation of the mutation of interest as the only variable within the experimental model 110 In one such report kidney organoids derived from iPSC of a patient with Mainzer Saldino Syndrome due to compound heterozygous mutations in IFT140 were compared to an isogenic control organoid in which an IFT140 variant giving rise to a non viable mRNA transcript was corrected by CRISPR 108 Patient kidney organoids demonstrated abnormal ciliary morphology consistent with existing animal models which was rescued to wild type morphology in the gene corrected organoids 108 Comparative transcriptional profiling of epithelial cells purified from patient and control organoids highlighted pathways involved in cell polarity cell cell junctions and dynein motor assembly some of which had been implicated for other genotypes within the phenotypic family of renal ciliopathies 108 Another report utilising an isogenic control demonstrated abnormal nephrin localisation in the glomeruli of kidney organoids generated from a patient with congenital nephrotic syndrome 109 Things such as epithelial metabolism can also be modelled 111 Personalised medicine editIntestinal organoids grown from rectal biopsies using culture protocols established by the Clevers group have been used to model cystic fibrosis 112 and led to the first application of organoids for personalised treatment 113 Cystic fibrosis is an inherited disease that is caused by gene mutations of the cystic fibrosis transmembrane conductance regulator gene that encodes an epithelial ion channel necessary for healthy epithelial surface fluids Studies by the laboratory of Jeffrey Beekman Wilhelmina Children s Hospital University Medical Center Utrecht The Netherlands described in 2013 that stimulation of colorectal organoids with cAMP raising agonists such as forskolin or cholera toxin induced rapid swelling of organoids in a fully CFTR dependent manner 112 Whereas organoids from non cystic fibrosis subjects swell in response to forskolin as a consequence of fluid transport into the organoids lumens this is severely reduced or absent in organoids derived from people with cystic fibrosis Swelling could be restored by therapeutics that repair the CFTR protein CFTR modulators indicating that individual responses to CFTR modulating therapy could be quantitated in a preclinical laboratory setting Schwank et al also demonstrated that the intestinal cystic fibrosis organoid phenotype could be repaired by CRISPR Cas9 gene editing in 2013 114 Follow up studies by Dekkers et al in 2016 revealed that quantitative differences in forskolin induced swelling between intestinal organoids derived from people with cystic fibrosis associate with known diagnostic and prognostic markers such as CFTR gene mutations or in vivo biomarkers of CFTR function 113 In addition the authors demonstrated that CFTR modulator responses in intestinal organoids with specific CFTR mutations correlated with published clinical trial data of these treatments This led to preclinical studies where organoids from patients with extremely rare CFTR mutations for who no treatment was registered were found to respond strongly to a clinically available CFTR modulator The suggested clinical benefit of treatment for these subjects based on the preclinical organoid test was subsequently confirmed upon clinical introduction of treatment by members of the clinical CF center under supervision of Kors van der Ent Department of Paediatric Pulmonology Wilhelmina Children s Hospital University Medical Center Utrecht The Netherlands These studies show for the first time that organoids can be used for the individual tailoring of therapy or personalised medicine Organoid transplants editThe first successful transplantation of an organoid into a human a patient with ulcerative colitis whose cells were used for the organoid was carried out in 2022 115 116 As a model for developmental biology editOrganoids offer researchers an exceptional model to study developmental biology 117 Since the identification of pluripotent stem cells there have been great advancements in directing pluripotent stem cells fate in vitro using 2D cultures 117 These advancements in PSC fate direction coupled with the advancements in 3D culturing techniques allowed for the creation of organoids that recapitulate the properties of various specific subregions of a multitude of organs 117 The use of these organoids has thus greatly contributed to expanding our understanding of the processes of organogenesis and the field of developmental biology 117 In central nervous system development for example organoids have contributed to our understanding of the physical forces that underlie retinal cup formation 117 118 More recent work has extended cortical organoid growth periods extensively and at nearly a year under specific differentiation conditions the organoids persist and have some features of human fetal development stages 119 See also editArtificial organ Organ cultureReferences edit Zhao Z Chen X Dowbaj AM Sljukic A Bratlie K Lin L Fong ELS Balachander GM Chen Z Soragni A Huch M Zeng YA Wang Q Yu H Organoids Nature Reviews Methods Primers 2 94 2022 https doi org 10 1038 s43586 022 00174 y Grens K December 24 2013 2013 s Big Advances in Science The Scientist Retrieved 26 December 2013 Hans Clevers Asher Mullard Mini organs attract big pharma Nature Reviews Drug Discovery 16 February 2023 https doi org 10 1038 d41573 023 00030 y a b c d e f g h i j k l m n o p q Lancaster MA Knoblich JA July 2014 Organogenesis in a dish modeling development and disease using organoid technologies Science 345 6194 1247125 doi 10 1126 science 1247125 PMID 25035496 S2CID 16105729 Wilson HV June 1907 A new method by which sponges may be artificially reared Science 25 649 912 5 Bibcode 1907Sci 25 912W doi 10 1126 science 25 649 912 PMID 17842577 Holtfreter J 1944 Experimental studies on the development of the pronephros Rev Can Biol 3 220 250 Weiss P Taylor AC September 1960 Reconstitution of complete organs from single cell suspensions of chick embryos in advanced stages of differentiation Proceedings of the National Academy of Sciences of the United States of America 46 9 1177 85 Bibcode 1960PNAS 46 1177W doi 10 1073 pnas 46 9 1177 PMC 223021 PMID 16590731 Rheinwald James G Green Howard November 1975 Formation of a keratinizing epithelium in culture by a cloned cell line derived from a teratoma Cell 6 3 317 330 doi 10 1016 0092 8674 75 90183 x ISSN 0092 8674 PMID 1052770 S2CID 28185779 a b Yi Sang Ah Zhang Yixiao Rathnam Christopher Pongkulapa Thanapat Lee Ki Bum November 2021 Bioengineering Approaches for the Advanced Organoid Research Advanced Materials 33 45 e2007949 Bibcode 2021AdM 3307949Y doi 10 1002 adma 202007949 ISSN 0935 9648 PMC 8682947 PMID 34561899 Li M L Aggeler J Farson D A Hatier C Hassell J Bissell M J January 1987 Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells Proceedings of the National Academy of Sciences 84 1 136 140 Bibcode 1987PNAS 84 136L doi 10 1073 pnas 84 1 136 ISSN 0027 8424 PMC 304157 PMID 3467345 Barcellos Hoff M H Aggeler J Ram T G Bissell M J 1989 02 01 Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane Development 105 2 223 235 doi 10 1242 dev 105 2 223 ISSN 0950 1991 PMC 2948482 PMID 2806122 Streuli C H Schmidhauser C Bailey N Yurchenco P Skubitz A P Roskelley C Bissell M J 1995 05 01 Laminin mediates tissue specific gene expression in mammary epithelia The Journal of Cell Biology 129 3 591 603 doi 10 1083 jcb 129 3 591 ISSN 0021 9525 PMC 2120432 PMID 7730398 Nahmias Y Schwartz RE Hu WS Verfaillie CM Odde DJ June 2006 Endothelium mediated hepatocyte recruitment in the establishment of liver like tissue in vitro Tissue Engineering 12 6 1627 38 doi 10 1089 ten 2006 12 1627 PMID 16846358 Yong E August 28 2013 Lab Grown Model Brains The Scientist Retrieved 26 December 2013 a b c d e Sato T Vries RG Snippert HJ van de Wetering M Barker N Stange DE et al May 2009 Single Lgr5 stem cells build crypt villus structures in vitro without a mesenchymal niche Nature 459 7244 262 5 Bibcode 2009Natur 459 262S doi 10 1038 nature07935 PMID 19329995 S2CID 4373784 a b Unbekandt M Davies JA March 2010 Dissociation of embryonic kidneys followed by reaggregation allows the formation of renal tissues Kidney International 77 5 407 16 doi 10 1038 ki 2009 482 PMID 20016472 Peng H Poovaiah N Forrester M Cochran E Wang Q Ex Vivo Culture of Primary Intestinal Stem Cells in Collagen Gels and Foams ACS Biomaterials Science amp Engineering 2014 Dec 2 1 1 37 42 https doi org 10 1021 ab500041d PMID 33435081 Peng H Wang C Xu X Yu C Wang Q An intestinal Trojan horse for gene delivery Nanoscale 2015 Jan 6 7 10 4354 4360 https doi org 10 1039 C4NR06377E PMID 25619169 Lawrence ML Chang CH Davies JA March 2015 Transport of organic anions and cations in murine embryonic kidney development and in serially reaggregated engineered kidneys Scientific Reports 5 9092 Bibcode 2015NatSR 5E9092L doi 10 1038 srep09092 PMC 4357899 PMID 25766625 Xinaris C Benedetti V Rizzo P Abbate M Corna D Azzollini N et al November 2012 In vivo maturation of functional renal organoids formed from embryonic cell suspensions Journal of the American Society of Nephrology 23 11 1857 68 doi 10 1681 ASN 2012050505 PMC 3482737 PMID 23085631 Yui S Nakamura T Sato T et al Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5 stem cell Nature Medicine 18 618 623 2012 https doi org 10 1038 nm 2695 a b c Lancaster MA Renner M Martin CA Wenzel D Bicknell LS Hurles ME et al September 2013 Cerebral organoids model human brain development and microcephaly Nature 501 7467 373 9 Bibcode 2013Natur 501 373L doi 10 1038 nature12517 PMC 3817409 PMID 23995685 Huch M Dorrell C Boj S et al In vitro expansion of single Lgr5 liver stem cells induced by Wnt driven regeneration Nature 494 247 250 2013 https doi org 10 1038 nature11826 Shkumatov A Baek K Kong H 2014 Matrix rigidity modulated cardiovascular organoid formation from embryoid bodies PLOS ONE 9 4 e94764 Bibcode 2014PLoSO 994764S doi 10 1371 journal pone 0094764 PMC 3986240 PMID 24732893 Takebe T Enomura M Yoshizawa E Kimura M Koike H Ueno Y et al May 2015 Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell Driven Condensation Cell Stem Cell 16 5 556 65 doi 10 1016 j stem 2015 03 004 PMID 25891906 Murry Charles E Keller Gordon February 2008 Differentiation of Embryonic Stem Cells to Clinically Relevant Populations Lessons from Embryonic Development Cell 132 4 661 680 doi 10 1016 j cell 2008 02 008 ISSN 0092 8674 PMID 18295582 Choudhury Deepak Ashok Aswathi Naing May Win March 2020 Commercialization of Organoids Trends in Molecular Medicine 26 3 245 249 doi 10 1016 j molmed 2019 12 002 ISSN 1471 4914 PMID 31982341 S2CID 210922708 Li ML Aggeler J Farson DA Hatier C Hassell J Bissell MJ January 1987 Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells Proceedings of the National Academy of Sciences of the United States of America 84 1 136 40 Bibcode 1987PNAS 84 136L doi 10 1073 pnas 84 1 136 PMC 304157 PMID 3467345 a b c Pastula A Middelhoff M Brandtner A Tobiasch M Hohl B Nuber AH et al 2016 Three Dimensional Gastrointestinal Organoid Culture in Combination with Nerves or Fibroblasts A Method to Characterize the Gastrointestinal Stem Cell Niche Stem Cells International 2016 3710836 doi 10 1155 2016 3710836 PMC 4677245 PMID 26697073 Takahashi Kazutoshi Yamanaka Shinya August 2006 Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors Cell 126 4 663 676 doi 10 1016 j cell 2006 07 024 hdl 2433 159777 ISSN 0092 8674 PMID 16904174 Ran F Ann Hsu Patrick D Wright Jason Agarwala Vineeta Scott David A Zhang Feng 2013 10 24 Genome engineering using the CRISPR Cas9 system Nature Protocols 8 11 2281 2308 doi 10 1038 nprot 2013 143 ISSN 1754 2189 PMC 3969860 PMID 24157548 Lavazza A Massimini M September 2018 Cerebral organoids ethical issues and consciousness assessment Journal of Medical Ethics 44 9 606 610 doi 10 1136 medethics 2017 104555 PMID 29491041 Prosser Scully Ruby 6 July 2019 Miniature brains grown in the lab have human like neural activity New Scientist No 3237 Sample Ian 21 October 2019 Scientists may have crossed ethical line in growing human brains The Guardian p 15 Cai H Ao Z Tian C et al Brain organoid reservoir computing for artificial intelligence Nat Electron 2023 https doi org 10 1038 s41928 023 01069 w Smirnova L Caffo BS Gracias DH Huang Q Morales Pantoja IE Tang B Zack DJ Berlinicke CA Boyd JL Harris TD Johnson EC Kagan BJ Kahn J Muotri AR Paulhamus BL Schwamborn JC Plotkin J Szalay AS Vogelstein JT Worley PF and Hartung T Organoid intelligence OI the new frontier in biocomputing and intelligence in a dish Front Sci 2023 1 1017235 https doi org 10 3389 fsci 2023 1017235 Sato Toshiro Stange Daniel E Ferrante Marc Vries Robert G J van Es Johan H van den Brink Stieneke van Houdt Winan J Pronk Apollo van Gorp Joost Siersema Peter D Clevers Hans November 2011 Long term Expansion of Epithelial Organoids From Human Colon Adenoma Adenocarcinoma and Barrett s Epithelium Gastroenterology 141 5 1762 1772 doi 10 1053 j gastro 2011 07 050 ISSN 0016 5085 PMID 21889923 Jung Peter Sato Toshiro Merlos Suarez Anna Barriga Francisco M Iglesias Mar Rossell David Auer Herbert Gallardo Mercedes Blasco Maria A Sancho Elena Clevers Hans October 2011 Isolation and in vitro expansion of human colonic stem cells Nature Medicine 17 10 1225 1227 doi 10 1038 nm 2470 ISSN 1078 8956 PMID 21892181 S2CID 205388154 Cai T Qi Y Jergens A Wannemuehler M Barrett TA Wang Q Effects of six common dietary nutrients on murine intestinal organoid growth PLoS One 2018 Feb 1 13 2 e0191517 https doi org 10 1371 journal pone 0191517 PMID 29389993 PMCID PMC5794098 Qi Y Lohman J Bratlie KM Peroutka Bigus N Bellaire B Wannemuehler M Yoon KJ Barrett TA Wang Q Vitamin C and B3 as new biomaterials to alter intestinal stem cells Journal of Biomedical Materials Research Part A 2019 Sep 107 9 1886 1897 https doi org 10 1002 jbm a 36715 Epub 2019 May 23 PMID 31071241 PMCID PMC6626554 Davoudi Z Peroutka Bigus N Bellaire B Wannemuehler M Barrett TA Narasimhan B Wang Q Intestinal organoids containing poly lactic co glycolic acid nanoparticles for the treatment of inflammatory bowel diseases Journal of Biomedical Materials Research Part A 2018 Apr 106 4 876 886 https doi org 10 1002 jbm a 36305 Epub 2017 Dec 21 PMID 29226615 PMCID PMC5826879 Davoudi Z Peroutka Bigus N Bellaire B Jergens A Wannemuehler M Wang Q Gut Organoid as a New Platform to Study Alginate and Chitosan Mediated PLGA Nanoparticles for Drug Delivery Marine Drugs 2021 May 20 19 5 282 https doi org 10 3390 md19050282 PMID 34065505 PMCID PMC8161322 Qi Y Shi E Peroutka Bigus N Bellaire B Wannemuehler M Jergens A Barrett T Wu Y Wang Q Ex Vivo Study of Telluride Nanowires in Minigut Journal of Biomedical Nanotechnology 2018 May 1 14 5 978 986 https doi org 10 1166 jbn 2018 2578 PMID 29883567 Reding B Carter P Qi Y Li Z Wu Y Wannemuehler M Bratlie KM Wang Q Manipulate intestinal organoids with niobium carbide nanosheets Journal of Biomedical Materials Research Part A 2021 Apr 109 4 479 487 https doi org 10 1002 jbm a 37032 Epub 2020 Jun 17 PMID 32506610 Zietek T Giesbertz P Ewers M Reichart F Weinmuller M Demir IE et al 2020 Organoids to Study Intestinal Nutrient Transport Drug Uptake and Metabolism Update to the Human Model and Expansion of Applications Frontiers in Bioengineering and Biotechnology 8 577656 doi 10 3389 fbioe 2020 577656 PMC 7516017 PMID 33015026 Zietek T Rath E Haller D Daniel H November 2015 Intestinal organoids for assessing nutrient transport sensing and incretin secretion Scientific Reports 5 1 16831 Bibcode 2015NatSR 516831Z doi 10 1038 srep16831 PMC 4652176 PMID 26582215 Rahmani Sara Breyner Natalia M Su Hsuan Ming Verdu Elena F Didar Tohid F 2019 02 01 Intestinal organoids A new paradigm for engineering intestinal epithelium in vitro Biomaterials 194 195 214 doi 10 1016 j biomaterials 2018 12 006 ISSN 0142 9612 PMID 30612006 S2CID 58603850 Sun L Rollins D Qi Y Fredericks J Mansell TJ Jergens A Phillips GJ Wannemuehler M Wang Q TNFa regulates intestinal organoids from mice with both defined and conventional microbiota International Journal of Biological Macromolecules 2020 Dec 1 164 548 556 https doi org 10 1016 j ijbiomac 2020 07 176 Epub 2020 Jul 18 PMID 32693143 PMCID PMC7657954 Tong T Qi Y Rollins D Bussiere LD Dhar D Miller CL Yu C Wang Q Rational design of oral drugs targeting mucosa delivery with gut organoid platforms Bioactive Materials 2023 30 116 128 https doi org 10 1016 j bioactmat 2023 07 014 PMID 37560199 Davoudi Z Atherly T Borcherding DC Jergens AE Wannemuehler M Barrett TA Wang Q Study Transportation of Drugs within Newly Established Murine Colon Organoid Systems Advanced Biology 2023 e2300103 https doi org 10 1002 adbi 202300103 PMID 37607116 Lindemans C Mertelsmann A Dudakov JA Velardi E Hua G O Connor M et al 2014 IL 22 Administration Protects Intestinal Stem Cells from Gvhd Biology of Blood and Marrow Transplantation 20 2 S53 S54 doi 10 1016 j bbmt 2013 12 056 Zhang Yong Guo Wu Shaoping Xia Yinglin Sun Jun September 2014 Salmonella infected crypt derived intestinal organoid culture system for host bacterial interactions Physiological Reports 2 9 e12147 doi 10 14814 phy2 12147 PMC 4270227 PMID 25214524 Geiser Petra Di Martino Maria Letizia Samperio Ventayol Pilar Eriksson Jens Sima Eduardo Al Saffar Anas Kh Ahl David Phillipson Mia Webb Dominic Luc Sundbom Magnus Hellstrom Per M 2021 02 23 Sperandio Vanessa ed Salmonella enterica Serovar Typhimurium Exploits Cycling through Epithelial Cells To Colonize Human and Murine Enteroids mBio 12 1 doi 10 1128 mBio 02684 20 ISSN 2161 2129 PMC 7844539 PMID 33436434 Dutta Devanjali Heo Inha O Connor Roberta 2019 09 14 Studying Cryptosporidium Infection in 3D Tissue derived Human Organoid Culture Systems by Microinjection Journal of Visualized Experiments 151 59610 doi 10 3791 59610 ISSN 1940 087X PMID 31566619 S2CID 203377662 Co Julia Y Margalef Catala Mar Li Xingnan Mah Amanda T Kuo Calvin J Monack Denise M Amieva Manuel R February 2019 Controlling Epithelial Polarity A Human Enteroid Model for Host Pathogen Interactions Cell Reports 26 9 2509 2520 e4 doi 10 1016 j celrep 2019 01 108 PMC 6391775 PMID 30811997 Tong T Qi Y Bussiere LD Wannemuehler M Miller CL Wang Q Yu C Transport of artificial virus like nanocarriers through intestinal monolayers via microfold cells Nanoscale 2020 Aug 14 12 30 16339 16347 https doi org 10 1039 D0NR03680C Epub 2020 Jul 29 PMID 32725029 a b Noel Gaelle Baetz Nicholas W Staab Janet F Donowitz Mark Kovbasnjuk Olga Pasetti Marcela F Zachos Nicholas C 2017 05 31 A primary human macrophage enteroid co culture model to investigate mucosal gut physiology and host pathogen interactions Scientific Reports 7 1 45270 Bibcode 2017NatSR 745270N doi 10 1038 srep45270 ISSN 2045 2322 PMC 5366908 PMID 28345602 Bouchi R Foo KS Hua H Tsuchiya K Ohmura Y Sandoval PR Ratner LE Egli D Leibel RL Accili D June 2014 FOXO1 inhibition yields functional insulin producing cells in human gut organoid cultures Nature Communications 5 4242 Bibcode 2014NatCo 5 4242B doi 10 1038 ncomms5242 PMC 4083475 PMID 24979718 Sontheimer Phelps Alexandra Chou David B Tovaglieri Alessio Ferrante Thomas C Duckworth Taylor Fadel Cicely Frismantas Viktoras Sutherland Arlene D Jalili Firoozinezhad Sasan Kasendra Magdalena Stas Eric 2020 Human Colon on a Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology Cellular and Molecular Gastroenterology and Hepatology 9 3 507 526 doi 10 1016 j jcmgh 2019 11 008 PMC 7036549 PMID 31778828 Grassart Alexandre Malarde Valerie Gobaa Samy Sartori Rupp Anna Kerns Jordan Karalis Katia Marteyn Benoit Sansonetti Philippe Sauvonnet Nathalie September 2019 Bioengineered Human Organ on Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection Cell Host amp Microbe 26 3 435 444 e4 doi 10 1016 j chom 2019 08 007 PMID 31492657 S2CID 201868491 a b c McCracken KW Cata EM Crawford CM Sinagoga KL Schumacher M Rockich BE et al December 2014 Modelling human development and disease in pluripotent stem cell derived gastric organoids Nature 516 7531 400 4 Bibcode 2014Natur 516 400M doi 10 1038 nature13863 PMC 4270898 PMID 25363776 Barker N Huch M Kujala P van de Wetering M Snippert HJ van Es JH et al January 2010 Lgr5 ve stem cells drive self renewal in the stomach and build long lived gastric units in vitro Cell Stem Cell 6 1 25 36 doi 10 1016 j stem 2009 11 013 PMID 20085740 Li X Nadauld L Ootani A Corney DC Pai RK Gevaert O et al July 2014 Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture Nature Medicine 20 7 769 77 doi 10 1038 nm 3585 PMC 4087144 PMID 24859528 a b Nadauld LD Garcia S Natsoulis G Bell JM Miotke L Hopmans ES et al August 2014 Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer Genome Biology 15 8 428 doi 10 1186 s13059 014 0428 9 PMC 4145231 PMID 25315765 a b Hisha H Tanaka T Kanno S Tokuyama Y Komai Y Ohe S et al November 2013 Establishment of a novel lingual organoid culture system generation of organoids having mature keratinized epithelium from adult epithelial stem cells Scientific Reports 3 3224 Bibcode 2013NatSR 3E3224H doi 10 1038 srep03224 PMC 3828633 PMID 24232854 a b Aihara E Mahe MM Schumacher MA Matthis AL Feng R Ren W et al November 2015 Characterization of stem progenitor cell cycle using murine circumvallate papilla taste bud organoid Scientific Reports 5 17185 Bibcode 2015NatSR 517185A doi 10 1038 srep17185 PMC 4665766 PMID 26597788 Ren W Lewandowski BC Watson J Aihara E Iwatsuki K Bachmanov AA Margolskee RF Jiang P November 2014 Single Lgr5 or Lgr6 expressing taste stem progenitor cells generate taste bud cells ex vivo Proceedings of the National Academy of Sciences of the United States of America 111 46 16401 6 Bibcode 2014PNAS 11116401R doi 10 1073 pnas 1409064111 PMC 4246268 PMID 25368147 Hermans F Hasevoets S Vankelecom H Bronckaers A Lambrichts I 18 March 2024 From Pluripotent Stem Cells to Organoids and Bioprinting Recent Advances in Dental Epithelium and Ameloblast Models to Study Tooth Biology and Regeneration Stem Cell Reviews and Reports doi 10 1007 s12015 024 10702 w PMID 38498295 Martin A Barbesino G Davies TF 1999 T cell receptors and autoimmune thyroid disease signposts for T cell antigen driven diseases International Reviews of Immunology 18 1 2 111 40 doi 10 3109 08830189909043021 PMID 10614741 Bredenkamp N Ulyanchenko S O Neill KE Manley NR Vaidya HJ Blackburn CC September 2014 An organized and functional thymus generated from FOXN1 reprogrammed fibroblasts Nature Cell Biology 16 9 902 8 doi 10 1038 ncb3023 PMC 4153409 PMID 25150981 a b c Vianello F Poznansky MC 2007 Generation of a tissue engineered thymic organoid Immunological Tolerance Methods in Molecular Biology Vol 380 pp 163 70 doi 10 1007 978 1 59745 395 0 9 ISBN 978 1 59745 395 0 PMID 17876092 Sakib Sadman et al 1 June 2019 Formation of organotypic testicular organoids in microwell culture Biology of Reproduction 100 6 1648 1660 doi 10 1093 biolre ioz053 PMC 7302515 PMID 30927418 Drost Jarno Karthaus Wouter R Gao Dong Driehuis Else Sawyers Charles L Chen Yu Clevers Hans 21 January 2016 Organoid culture systems for prostate epithelial and cancer tissue Nature Protocols 11 2 347 358 doi 10 1038 nprot 2016 006 ISSN 1750 2799 PMC 4793718 PMID 26797458 Huch M Gehart H van Boxtel R Hamer K Blokzijl F Verstegen MM et al January 2015 Long term culture of genome stable bipotent stem cells from adult human liver Cell 160 1 2 299 312 doi 10 1016 j cell 2014 11 050 PMC 4313365 PMID 25533785 Li P Li Y Wang Y Liu J Lavrijsen M Li Y Zhang R Verstegen MMA Wang Y Li TC Ma Z Kainov DE Bruno MJ de Man RA van der Laan LJW Peppelenbosch MP Pan Q 2022 Recapitulating hepatitis E virus host interactions and facilitating antiviral drug discovery in human liver derived organoids Science Advances 8 3 103 111 Bibcode 2022SciA 8 5908L doi 10 1126 sciadv abj5908 hdl 11250 3047921 PMID 5044825 S2CID 246069868 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Huch M Bonfanti P Boj SF Sato T Loomans CJ van de Wetering M et al October 2013 Unlimited in vitro expansion of adult bi potent pancreas progenitors through the Lgr5 R spondin axis The EMBO Journal 32 20 2708 21 doi 10 1038 emboj 2013 204 PMC 3801438 PMID 24045232 Hou S Tiriac H Sridharan BP Scampavia L Madoux F Seldin J et al 2018 Advanced Development of Primary Pancreatic Organoid Tumor Models for High Throughput Phenotypic Drug Screening SLAS Discov 23 6 574 584 doi 10 1177 2472555218766842 PMC 6013403 PMID 29673279 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Wolff RA Wang Gillam A Alvarez H Tiriac H Engle D Hou S et al 2018 Dynamic changes during the treatment of pancreatic cancer Oncotarget 9 19 14764 14790 doi 10 18632 oncotarget 24483 PMC 5871077 PMID 29599906 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Below Christopher R Kelly Joanna Brown Alexander Humphries Jonathan D Hutton Colin Xu Jingshu Lee Brian Y Cintas Celia Zhang Xiaohong Hernandez Gordillo Victor Stockdale Linda 2021 09 13 A microenvironment inspired synthetic three dimensional model for pancreatic ductal adenocarcinoma organoids Nature Materials 21 1 110 119 doi 10 1038 s41563 021 01085 1 ISSN 1476 4660 PMC 7612137 PMID 34518665 Barker N van Es JH Kuipers J Kujala P van den Born M Cozijnsen M et al October 2007 Identification of stem cells in small intestine and colon by marker gene Lgr5 Nature 449 7165 1003 7 Bibcode 2007Natur 449 1003B doi 10 1038 nature06196 PMID 17934449 S2CID 4349637 Lee JH Bhang DH Beede A Huang TL Stripp BR Bloch KD et al January 2014 Lung stem cell differentiation in mice directed by endothelial cells via a BMP4 NFATc1 thrombospondin 1 axis Cell 156 3 440 55 doi 10 1016 j cell 2013 12 039 PMC 3951122 PMID 24485453 Takasato M Er PX Chiu HS Maier B Baillie GJ Ferguson C et al October 2015 Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis Nature 526 7574 564 8 Bibcode 2015Natur 526 564T doi 10 1038 nature15695 PMID 26444236 S2CID 4443766 a b c Freedman BS Brooks CR Lam AQ Fu H Morizane R Agrawal V et al October 2015 Modelling kidney disease with CRISPR mutant kidney organoids derived from human pluripotent epiblast spheroids Nature Communications 6 8715 Bibcode 2015NatCo 6 8715F doi 10 1038 ncomms9715 PMC 4620584 PMID 26493500 Morizane R Lam AQ Freedman BS Kishi S Valerius MT Bonventre JV November 2015 Nephron organoids derived from human pluripotent stem cells model kidney development and injury Nature Biotechnology 33 11 1193 200 doi 10 1038 nbt 3392 PMC 4747858 PMID 26458176 van den Brink SC Baillie Johnson P Balayo T Hadjantonakis AK Nowotschin S Turner DA et al November 2014 Symmetry breaking germ layer specification and axial organisation in aggregates of mouse embryonic stem cells Development 141 22 4231 42 doi 10 1242 dev 113001 PMC 4302915 PMID 25371360 Turner DA Baillie Johnson P Martinez Arias A February 2016 Organoids and the genetically encoded self assembly of embryonic stem cells BioEssays 38 2 181 91 doi 10 1002 bies 201500111 PMC 4737349 PMID 26666846 Turner DA Girgin M Alonso Crisostomo L Trivedi V Baillie Johnson P Glodowski CR et al November 2017 Anteroposterior polarity and elongation in the absence of extra embryonic tissues and of spatially localised signalling in gastruloids mammalian embryonic organoids Development 144 21 3894 3906 doi 10 1242 dev 150391 PMC 5702072 PMID 28951435 a b Beccari L Moris N Girgin M Turner DA Baillie Johnson P Cossy AC et al October 2018 Multi axial self organization properties of mouse embryonic stem cells into gastruloids Nature 562 7726 272 276 Bibcode 2018Natur 562 272B doi 10 1038 s41586 018 0578 0 PMID 30283134 S2CID 52915553 Blastoid The backstory of the formation of blastocyst like structure solely from stem cells 2018 06 27 Nicolas Rivron Lab Blastoid Netherlands Rivron NC Frias Aldeguer J Vrij EJ Boisset JC Korving J Vivie J et al May 2018 Blastocyst like structures generated solely from stem cells PDF Nature 557 7703 106 111 Bibcode 2018Natur 557 106R doi 10 1038 s41586 018 0051 0 PMID 29720634 S2CID 13749109 Rawlings TM Makwana K Tryfonos M Lucas ES July 2021 Organoids to model the endometrium implantation and beyond Reprod Fertil 2 3 R85 R101 doi 10 1530 RAF 21 0023 PMC 8801025 PMID 35118399 Lee EJ Kim DE Azeloglu EU Costa KD February 2008 Engineered cardiac organoid chambers toward a functional biological model ventricle Tissue Engineering Part A 14 2 215 25 doi 10 1089 tea 2007 0351 PMID 18333774 Molteni M 2018 06 27 These Beating Mini Hearts Could Save Big Bucks And Maybe Lives WIRED Retrieved 2018 06 30 Wiley LA Burnight ER DeLuca AP Anfinson KR Cranston CM Kaalberg EE et al July 2016 cGMP production of patient specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness Scientific Reports 6 30742 Bibcode 2016NatSR 630742W doi 10 1038 srep30742 PMC 4965859 PMID 27471043 Zilova Lucie Weinhardt Venera Tavhelidse Tinatini Schlagheck Christina Thumberger Thomas Wittbrodt Joachim 2021 07 12 Martinez Arias Alfonso Stainier Didier YR Martinez Arias Alfonso eds Fish primary embryonic pluripotent cells assemble into retinal tissue mirroring in vivo early eye development eLife 10 e66998 doi 10 7554 eLife 66998 ISSN 2050 084X PMC 8275126 PMID 34252023 Sachs Norman de Ligt Joep Kopper Oded Gogola Ewa Bounova Gergana Weeber Fleur Balgobind Anjali Vanita Wind Karin Gracanin Ana Begthel Harry Korving Jeroen van Boxtel Ruben Duarte Alexandra Alves Lelieveld Daphne et al 2018 A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity Cell 172 1 2 373 386 e10 doi 10 1016 j cell 2017 11 010 ISSN 0092 8674 PMID 29224780 van de Wetering Marc Francies Hayley Francis Joshua Bounova Gergana Iorio Francesco Pronk Apollo van Houdt Winan van Gorp Joost Taylor Weiner Amaro Kester Lennart McLaren Douglas Anne Blokker Joyce Jaksani Sridevi Bartfeld Sina et al 2015 Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients Cell 161 4 933 945 doi 10 1016 j cell 2015 03 053 ISSN 0092 8674 PMC 6428276 PMID 25957691 Quereda V Hou S Madoux F Scampavia L Spicer TP Duckett D 2018 A Cytotoxic Three Dimensional Spheroid High Throughput Assay Using Patient Derived Glioma Stem Cells SLAS Discov 23 8 842 849 doi 10 1177 2472555218775055 PMC 6102052 PMID 29750582 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Dayton Talya L Alcala Nicolas Moonen Laura den Hartigh Lisanne Geurts Veerle Mangiante Lise Lap Lisa Dost Antonella F M Beumer Joep Levy Sonja van Leeuwaarde Rachel S Hackeng Wenzel M Samsom Kris Voegele Catherine et al 2023 Druggable growth dependencies and tumor evolution analysis in patient derived organoids of neuroendocrine neoplasms from multiple body sites Cancer Cell 41 12 2083 2099 doi 10 1016 j ccell 2023 11 007 ISSN 1535 6108 PMID 38086335 Zidaric Tanja Gradisnik Lidija Velnar Tomaz 2022 04 01 Astrocytes and human artificial blood brain barrier models Bosnian Journal of Basic Medical Sciences 22 5 651 672 doi 10 17305 bjbms 2021 6943 ISSN 1840 4812 PMC 9519155 PMID 35366791 Zietek T Rath E Haller D Daniel H November 2015 Intestinal organoids for assessing nutrient transport sensing and incretin secretion Scientific Reports 5 16831 Bibcode 2015NatSR 516831Z doi 10 1038 srep16831 PMC 4652176 PMID 26582215 a b c Cruz NM Song X Czerniecki SM Gulieva RE Churchill AJ Kim YK et al November 2017 Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease Nature Materials 16 11 1112 1119 Bibcode 2017NatMa 16 1112C doi 10 1038 nmat4994 PMC 5936694 PMID 28967916 a b c Kim YK Refaeli I Brooks CR Jing P Gulieva RE Hughes MR et al December 2017 Gene Edited Human Kidney Organoids Reveal Mechanisms of Disease in Podocyte Development Stem Cells 35 12 2366 2378 doi 10 1002 stem 2707 PMC 5742857 PMID 28905451 Takahashi K Tanabe K Ohnuki M Narita M Ichisaka T Tomoda K et al November 2007 Induction of pluripotent stem cells from adult human fibroblasts by defined factors PDF Cell 131 5 861 72 doi 10 1016 j cell 2007 11 019 hdl 2433 49782 PMID 18035408 S2CID 8531539 a b c Hsieh WC Ramadesikan S Fekete D Aguilar RC 2018 02 14 Kidney differentiated cells derived from Lowe Syndrome patient s iPSCs show ciliogenesis defects and Six2 retention at the Golgi complex PLOS ONE 13 2 e0192635 Bibcode 2018PLoSO 1392635H doi 10 1371 journal pone 0192635 PMC 5812626 PMID 29444177 Howden SE Thomson JA Little MH May 2018 Simultaneous reprogramming and gene editing of human fibroblasts Nature Protocols 13 5 875 898 doi 10 1038 nprot 2018 007 PMC 5997775 PMID 29622803 a b c d Forbes TA Howden SE Lawlor K Phipson B Maksimovic J Hale L et al May 2018 Patient iPSC Derived Kidney Organoids Show Functional Validation of a Ciliopathic Renal Phenotype and Reveal Underlying Pathogenetic Mechanisms American Journal of Human Genetics 102 5 816 831 doi 10 1016 j ajhg 2018 03 014 PMC 5986969 PMID 29706353 a b Tanigawa S Islam M Sharmin S Naganuma H Yoshimura Y Haque F et al September 2018 Organoids from Nephrotic Disease Derived iPSCs Identify Impaired NEPHRIN Localization and Slit Diaphragm Formation in Kidney Podocytes Stem Cell Reports 11 3 727 740 doi 10 1016 j stemcr 2018 08 003 PMC 6135868 PMID 30174315 Engle SJ Blaha L Kleiman RJ November 2018 Best Practices for Translational Disease Modeling Using Human iPSC Derived Neurons Neuron 100 4 783 797 doi 10 1016 j neuron 2018 10 033 PMID 30465765 Metabolites www mdpi com Retrieved 2022 10 16 a b Dekkers JF Wiegerinck CL de Jonge HR Bronsveld I Janssens HM de Winter de Groot KM et al July 2013 A functional CFTR assay using primary cystic fibrosis intestinal organoids Nature Medicine 19 7 939 45 doi 10 1038 nm 3201 PMID 23727931 S2CID 5369669 a b Dekkers JF Berkers G Kruisselbrink E Vonk A de Jonge HR Janssens HM et al June 2016 Characterizing responses to CFTR modulating drugs using rectal organoids derived from subjects with cystic fibrosis Science Translational Medicine 8 344 344ra84 doi 10 1126 scitranslmed aad8278 PMID 27334259 S2CID 19462535 Schwank G Koo BK Sasselli V Dekkers JF Heo I Demircan T et al December 2013 Functional repair of CFTR by CRISPR Cas9 in intestinal stem cell organoids of cystic fibrosis patients Cell Stem Cell 13 6 653 8 doi 10 1016 j stem 2013 11 002 PMID 24315439 World s first mini organ transportation to a patient with ulcerative colitis Tokyo Medical and Dental University via medicalxpress com Retrieved 18 September 2022 Watanabe Satoshi Kobayashi Sakurako Ogasawara Nobuhiko Okamoto Ryuichi Nakamura Tetsuya Watanabe Mamoru Jensen Kim B Yui Shiro March 2022 Transplantation of intestinal organoids into a mouse model of colitis Nature Protocols 17 3 649 671 doi 10 1038 s41596 021 00658 3 ISSN 1750 2799 PMID 35110738 S2CID 246488596 a b c d e Ader M Tanaka EM December 2014 Modeling human development in 3D culture Current Opinion in Cell Biology 31 23 8 doi 10 1016 j ceb 2014 06 013 PMID 25033469 Martinez Morales JR Cavodeassi F Bovolenta P 2017 Coordinated Morphogenetic Mechanisms Shape the Vertebrate Eye Frontiers in Neuroscience 11 721 doi 10 3389 fnins 2017 00721 PMC 5742352 PMID 29326547 Gordon Aaron Yoon Se Jin Tran Stephen S Makinson Christopher D Park Jin Young Andersen Jimena Valencia Alfredo M Horvath Steve Xiao Xinshu Huguenard John R Pașca Sergiu P 2021 02 22 Long term maturation of human cortical organoids matches key early postnatal transitions Nature Neuroscience 24 3 331 342 doi 10 1038 s41593 021 00802 y ISSN 1546 1726 PMC 8109149 PMID 33619405 Further reading editWillyard C July 2015 The boom in mini stomachs brains breasts kidneys and more Nature 523 7562 520 2 Bibcode 2015Natur 523 520W doi 10 1038 523520a PMID 26223610 Kelly Rae Chi 2015 Orchestrating Organoids A guide to crafting tissues in a dish that reprise in vivo organs The Scientist Takebe T Enomura M Yoshizawa E Kimura M Koike H Ueno Y Matsuzaki T Yamazaki T Toyohara T Osafune K Nakauchi H Yoshikawa HY Taniguchi H May 2015 Vascularized and Complex Organ Buds from Diverse Tissues via Mesenchymal Cell Driven Condensation Cell Stem Cell 16 5 556 65 doi 10 1016 j stem 2015 03 004 PMID 25891906 Turner DA Baillie Johnson P Martinez Arias A February 2016 Organoids and the genetically encoded self assembly of embryonic stem cells BioEssays 38 2 181 91 doi 10 1002 bies 201500111 PMC 4737349 PMID 26666846 Organoid based regenerative medicine Retrieved from https en wikipedia org w index php title Organoid amp oldid 1218565426, wikipedia, wiki, book, books, library,

article

, read, download, free, free download, mp3, video, mp4, 3gp, jpg, jpeg, gif, png, picture, music, song, movie, book, game, games.