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Regenerative medicine

December 14, 2023

Regenerative medicine deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function".[1] This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.[2]

A colony of human embryonic stem cells

Regenerative medicine also includes the possibility of growing tissues and organs in the laboratory and implanting them when the body cannot heal itself. When the cell source for a regenerated organ is derived from the patient's own tissue or cells,[3] the challenge of organ transplant rejection via immunological mismatch is circumvented.[4][5][6] This approach could alleviate the problem of the shortage of organs available for donation.

Some of the biomedical approaches within the field of regenerative medicine may involve the use of stem cells.[7] Examples include the injection of stem cells or progenitor cells obtained through directed differentiation (cell therapies); the induction of regeneration by biologically active molecules administered alone or as a secretion by infused cells (immunomodulation therapy); and transplantation of in vitro grown organs and tissues (tissue engineering).[8][9]

History edit

The ancient Greeks postulated whether parts of the body could be regenerated in the 700s BC.[10] Skin grafting, invented in the late 19th century, can be thought of as the earliest major attempt to recreate bodily tissue to restore structure and function.[11] Advances in transplanting body parts in the 20th century further pushed the theory that body parts could regenerate and grow new cells. These advances led to tissue engineering, and from this field, the study of regenerative medicine expanded and began to take hold.[10] This began with cellular therapy, which led to the stem cell research that is widely being conducted today.[12]

The first cell therapies were intended to slow the aging process. This began in the 1930s with Paul Niehans, a Swiss doctor who was known to have treated famous historical figures such as Pope Pius XII, Charlie Chaplin, and king Ibn Saud of Saudi Arabia. Niehans would inject cells of young animals (usually lambs or calves) into his patients in an attempt to rejuvenate them.[13][14] In 1956, a more sophisticated process was created to treat leukemia by inserting bone marrow from a healthy person into a patient with leukemia. This process worked mostly due to both the donor and receiver in this case being identical twins. Nowadays, bone marrow can be taken from people who are similar enough to the patient who needs the cells to prevent rejection.[15]

The term "regenerative medicine" was first used in a 1992 article on hospital administration by Leland Kaiser. Kaiser's paper closes with a series of short paragraphs on future technologies that will impact hospitals. One paragraph had "Regenerative Medicine" as a bold print title and stated, "A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems."[16][17]

The term was brought into the popular culture in 1999 by William A. Haseltine when he coined the term during a conference on Lake Como, to describe interventions that restore to normal function that which is damaged by disease, injured by trauma, or worn by time.[18] Haseltine was briefed on the project to isolate human embryonic stem cells and embryonic germ cells at Geron Corporation in collaboration with researchers at the University of Wisconsin–Madison and Johns Hopkins School of Medicine. He recognized that these cells' unique ability to differentiate into all the cell types of the human body (pluripotency) had the potential to develop into a new kind of regenerative therapy.[19][20] Explaining the new class of therapies that such cells could enable, he used the term "regenerative medicine" in the way that it is used today: "an approach to therapy that ... employs human genes, proteins and cells to re-grow, restore or provide mechanical replacements for tissues that have been injured by trauma, damaged by disease or worn by time" and "offers the prospect of curing diseases that cannot be treated effectively today, including those related to aging".[21][22]

Later, Haseltine would go on to explain that regenerative medicine acknowledges the reality that most people, regardless of which illness they have or which treatment they require, simply want to be restored to normal health. Designed to be applied broadly, the original definition includes cell and stem cell therapies, gene therapy, tissue engineering, genomic medicine, personalized medicine, biomechanical prosthetics, recombinant proteins, and antibody treatments. It also includes more familiar chemical pharmacopeia—in short, any intervention that restores a person to normal health. In addition to functioning as shorthand for a wide range of technologies and treatments, the term “regenerative medicine” is also patient friendly. It solves the problem that confusing or intimidating language discourages patients.

The term regenerative medicine is increasingly conflated with research on stem cell therapies. Some academic programs and departments retain the original broader definition while others use it to describe work on stem cell research.[23]

From 1995 to 1998 Michael D. West, PhD, organized and managed the research between Geron Corporation and its academic collaborators James Thomson at the University of Wisconsin–Madison and John Gearhart of Johns Hopkins University that led to the first isolation of human embryonic stem and human embryonic germ cells, respectively.[24]

In March 2000, Haseltine, Antony Atala, M.D., Michael D. West, Ph.D., and other leading researchers founded E-Biomed: The Journal of Regenerative Medicine.[25] The peer-reviewed journal facilitated discourse around regenerative medicine by publishing innovative research on stem cell therapies, gene therapies, tissue engineering, and biomechanical prosthetics. The Society for Regenerative Medicine, later renamed the Regenerative Medicine and Stem Cell Biology Society, served a similar purpose, creating a community of like-minded experts from around the world.[26]

In June 2008, at the Hospital Clínic de Barcelona, Professor Paolo Macchiarini and his team, of the University of Barcelona, performed the first tissue engineered trachea (wind pipe) transplantation. Adult stem cells were extracted from the patient's bone marrow, grown into a large population, and matured into cartilage cells, or chondrocytes, using an adaptive method originally devised for treating osteoarthritis. The team then seeded the newly grown chondrocytes, as well as epithelial cells, into a decellularised (free of donor cells) tracheal segment that was donated from a 51-year-old transplant donor who had died of cerebral hemorrhage. After four days of seeding, the graft was used to replace the patient's left main bronchus. After one month, a biopsy elicited local bleeding, indicating that the blood vessels had already grown back successfully.[27][28]

In 2009, the SENS Foundation was launched, with its stated aim as "the application of regenerative medicine – defined to include the repair of living cells and extracellular material in situ – to the diseases and disabilities of ageing".[29] In 2012, Professor Paolo Macchiarini and his team improved upon the 2008 implant by transplanting a laboratory-made trachea seeded with the patient's own cells.[30]

On September 12, 2014, surgeons at the Institute of Biomedical Research and Innovation Hospital in Kobe, Japan, transplanted a 1.3 by 3.0 millimeter sheet of retinal pigment epithelium cells, which were differentiated from iPS cells through directed differentiation, into an eye of an elderly woman, who suffers from age-related macular degeneration.[31]

In 2016, Paolo Macchiarini was fired from Karolinska University in Sweden due to falsified test results and lies.[32] The TV-show Experimenten aired on Swedish Television and detailed all the lies and falsified results.[33]

Research edit

Widespread interest and funding for research on regenerative medicine has prompted institutions in the United States and around the world to establish departments and research institutes that specialize in regenerative medicine including: The Department of Rehabilitation and Regenerative Medicine at Columbia University, the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University, the Center for Regenerative and Nanomedicine at Northwestern University, the Wake Forest Institute for Regenerative Medicine, and the British Heart Foundation Centers of Regenerative Medicine at the University of Oxford.[34][35][36][37] In China, institutes dedicated to regenerative medicine are run by the Chinese Academy of Sciences, Tsinghua University, and the Chinese University of Hong Kong, among others.[38][39][40]

In dentistry edit

 
A diagram of a human tooth. Stem cells are located in the pulp in the center.[41]

Regenerative medicine has been studied by dentists to find ways that damaged teeth can be repaired and restored to obtain natural structure and function.[42] Dental tissues are often damaged due to tooth decay, and are often deemed to be irreplaceable except by synthetic or metal dental fillings or crowns, which requires further damage to be done to the teeth by drilling into them to prevent the loss of an entire tooth.

Researchers from King's College London have created a drug called Tideglusib that claims to have the ability to regrow dentin, the second layer of the tooth beneath the enamel which encases and protects the pulp (often referred to as the nerve).[43]

Animal studies conducted on mice in Japan in 2007 show great possibilities in regenerating an entire tooth. Some mice had a tooth extracted and the cells from bioengineered tooth germs were implanted into them and allowed to grow. The result were perfectly functioning and healthy teeth, complete with all three layers, as well as roots. These teeth also had the necessary ligaments to stay rooted in its socket and allow for natural shifting. They contrast with traditional dental implants, which are restricted to one spot as they are drilled into the jawbone.[44][45]

A person's baby teeth are known to contain stem cells that can be used for regeneration of the dental pulp after a root canal treatment or injury. These cells can also be used to repair damage from periodontitis, an advanced form of gum disease that causes bone loss and severe gum recession. Research is still being done to see if these stem cells are viable enough to grow into completely new teeth. Some parents even opt to keep their children's baby teeth in special storage with the thought that, when older, the children could use the stem cells within them to treat a condition.[46][47]

Extracellular matrix edit

Extracellular matrix materials are commercially available and are used in reconstructive surgery, treatment of chronic wounds, and some orthopedic surgeries; as of January 2017 clinical studies were under way to use them in heart surgery to try to repair damaged heart tissue.[48][49]

The use of fish skin with its natural constituent of omega 3, has been developed by an Icelandic company Kereceis.[50] Omega 3 is a natural anti-inflammatory, and the fish skin material acts as a scaffold for cell regeneration.[51][52] In 2016 their product Omega3 Wound was approved by the FDA for the treatment of chronic wounds and burns.[51] In 2021 the FDA gave approval for Omega3 Surgibind to be used in surgical applications including plastic surgery.[53]

Cord blood edit

Though uses of cord blood beyond blood and immunological disorders is speculative, some research has been done in other areas.[54] Any such potential beyond blood and immunological uses is limited by the fact that cord cells are hematopoietic stem cells (which can differentiate only into blood cells), and not pluripotent stem cells (such as embryonic stem cells, which can differentiate into any type of tissue). Cord blood has been studied as a treatment for diabetes.[55] However, apart from blood disorders, the use of cord blood for other diseases is not a routine clinical modality and remains a major challenge for the stem cell community.[54][55]

Along with cord blood, Wharton's jelly and the cord lining have been explored as sources for mesenchymal stem cells (MSC),[56] and as of 2015 had been studied in vitro, in animal models, and in early stage clinical trials for cardiovascular diseases,[57] as well as neurological deficits, liver diseases, immune system diseases, diabetes, lung injury, kidney injury, and leukemia.[58]

See also edit

References edit

  1. ^ Mason, Chris; Dunnill, Peter (2008). "A brief definition of regenerative medicine". Regenerative Medicine. 3 (1): 1–5. doi:10.2217/17460751.3.1.1. ISSN 1746-0751. PMID 18154457.
  2. ^ "UM Leads in the Field of Regenerative Medicine: Moving from Treatments to Cures - Healthcanal.com". 8 May 2014.
  3. ^ Mahla RS (2016). "Stem cells application in regenerative medicine and disease threpeutics". International Journal of Cell Biology. 2016 (7): 1–24. doi:10.1155/2016/6940283. PMC 4969512. PMID 27516776.
  4. ^ (PDF). September 2006. Archived from the original (PDF) on 2011-10-26. Retrieved 2010-08-16.
  5. ^ Mason C; Dunnill P (January 2008). "A brief definition of regenerative medicine". Regenerative Medicine. 3 (1): 1–5. doi:10.2217/17460751.3.1.1. PMID 18154457.
  6. ^ "Regenerative medicine glossary". Regenerative Medicine. 4 (4 Suppl): S1–88. July 2009. doi:10.2217/rme.09.s1. PMID 19604041.
  7. ^ Riazi AM; Kwon SY; Stanford WL (2009). "Stem Cell Sources for Regenerative Medicine". Stem Cells in Regenerative Medicine. Methods in Molecular Biology. Vol. 482. pp. 55–90. doi:10.1007/978-1-59745-060-7_5. ISBN 978-1-58829-797-6. PMID 19089350.
  8. ^ Stoick-Cooper CL; Moon RT; Weidinger G (June 2007). "Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine". Genes & Development. 21 (11): 1292–315. doi:10.1101/gad.1540507. PMID 17545465.
  9. ^ Muneoka K; Allan CH; Yang X; Lee J; Han M (December 2008). "Mammalian regeneration and regenerative medicine". Birth Defects Research. Part C, Embryo Today. 84 (4): 265–80. doi:10.1002/bdrc.20137. PMID 19067422.
  10. ^ a b "What is Regenerative Medicine?". University of Nebraska Medical Center. University of Nebraska. Retrieved 27 June 2020.
  11. ^ Rahlf, Sidsel Hald (2009). "The Use of Skin Grafting for the Treatment of Burn Wounds in Denmark 1870-1960". Dansk Medicinhistorisk Arbog. 37: 99–116. PMID 20509454. Retrieved June 27, 2020.
  12. ^ Sampogna, Gianluca; Guraya, Salman Yousuf; Forgione, Atonello (September 2015). "Regenerative medicine: Historical roots and potential strategies in modern medicine". Journal of Microscopy and Ultrastructure. 3 (3): 101–107. doi:10.1016/j.jmau.2015.05.002. PMC 6014277. PMID 30023189.
  13. ^ "Dr. Paul Niehans, Swiss Surgeon, 89". The New York Times. September 4, 1971. Retrieved 27 June 2020. Dr. Paul Niehans was a former physician of Pope Paul XII, among others. A surgeon who performed more than 50,000 operations in 40 years, he developed his own rejuvenation treatment by injecting humans with the foetus of unborn lambs and other animals.
  14. ^ Milton, Joyce (1998). Tramp: The Life of Charlie Chaplin. HarperCollins. ISBN 0060170522.
  15. ^ . Home.cancerresearch. 7 December 2014. Archived from the original on 2 February 2020. Retrieved 26 July 2020.
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  17. ^ Lysaght MJ; Crager J (July 2009). "Origins". Tissue Engineering. Part A. 15 (7): 1449–50. doi:10.1089/ten.tea.2007.0412. PMID 19327019.
  18. ^ https://www.nsf.gov/pubs/2004/nsf0450/ Viola, J., Lal, B., and Grad, O. The Emergence of Tissue Engineering as a Research Field. Arlington, VA: National Science Foundation, 2003.
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  22. ^ Mao AS, Mooney DJ (Nov 2015). "Regenerative medicine: Current therapies and future directions". Proc Natl Acad Sci U S A. 112 (47): 14452–9. Bibcode:2015PNAS..11214452M. doi:10.1073/pnas.1508520112. PMC 4664309. PMID 26598661.
  23. ^ Sampogna, Gianluca; Guraya, Salman Yousuf; Forgione, Antonello (2015-09-01). "Regenerative medicine: Historical roots and potential strategies in modern medicine". Journal of Microscopy and Ultrastructure. 3 (3): 101–107. doi:10.1016/j.jmau.2015.05.002. ISSN 2213-879X. PMC 6014277. PMID 30023189.
  24. ^ . Archived from the original on 2013-08-03.
  25. ^ "E-Biomed: The Journal of Regenerative Medicine". E-Biomed. ISSN 1524-8909. Retrieved 2020-02-25.
  26. ^ Haseltine, William A (2011-07-01). "Interview: Commercial translation of cell-based therapies and regenerative medicine: learning by experience". Regenerative Medicine. 6 (4): 431–435. doi:10.2217/rme.11.40. ISSN 1746-0751. PMID 21749201.
  27. ^ "Tissue-Engineered Trachea Transplant Is Adult Stem Cell Breakthrough". Science 2.0. 2008-11-19. Retrieved 2010-03-19.
  28. ^ . Mirm.pitt.edu. Archived from the original on 2010-06-12. Retrieved 2010-03-19.
  29. ^ "Sens Foundation". sens.org. 2009-01-03. Retrieved 2012-02-23.
  30. ^ Fountain, Henry (2012-01-12). "Surgeons Implant Synthetic Trachea In Baltimore Man". The New York Times. Retrieved 2012-02-23.
  31. ^ Cyranoski, David (12 September 2014). "Japanese woman is first recipient of next-generation stem cells". Nature. doi:10.1038/nature.2014.15915. ISSN 0028-0836. S2CID 86969754.
  32. ^ Oltermann, Philip (2016-03-24). "'Superstar doctor' fired from Swedish institute over research 'lies'". The Guardian. ISSN 0261-3077. Retrieved 2017-10-13.
  33. ^ Sweden, Sveriges Television AB, Stockholm. "Experimenten". svt.se (in Swedish). Retrieved 2017-10-13.{{cite web}}: CS1 maint: multiple names: authors list (link)
  34. ^ "Research". Institute for Stem Cell Biologyand Regenerative Medicine. Retrieved 2020-02-25.
  35. ^ "CRN Origins and Mission | Center for Regenerative Nanomedicine, Northwestern University". crn.northwestern.edu. Retrieved 2020-02-25.
  36. ^ "Wake Forest Institute for Regenerative Medicine (WFIRM)". Wake Forest School of Medicine. Retrieved 2020-02-25.
  37. ^ "Centres of Regenerative Medicine". www.bhf.org.uk. Retrieved 2020-02-25.
  38. ^ "Guangzhou Institute of Biomedicine and Health,Chinese Academy of Sciences". english.gibh.cas.cn. Retrieved 2020-02-25.
  39. ^ . www.sps.tsinghua.edu.cn. Archived from the original on 2016-10-04. Retrieved 2020-02-25.
  40. ^ administrator. "Home". Institute for Tissue Engineering and Regenerative Medicine. Retrieved 2020-02-25.
  41. ^ Lan, Xiaoyan; Sun, Zhengwu; Chu, Chengyan; Boltze, Johannes; Li, Shen (2 August 2019). "Dental Pulp Stem Cells: An Attractive Alternative for Cell Therapy in Ischemic Stroke". Frontiers in Neurology. 10: 824. doi:10.3389/fneur.2019.00824. PMC 6689980. PMID 31428038. S2CID 199022265.
  42. ^ Steindorff, Marina M.; Lehl, Helena; Winkel, Andreas; Stiesch, Meike (February 2014). "Innovative approaches to regenerate teeth by tissue engineering". Archives of Oral Biology. 59 (2): 158–66. doi:10.1016/j.archoralbio.2013.11.005. PMID 24370187. Retrieved 27 June 2020.
  43. ^ King's College London (March 10, 2020). "Teeth That Repair Themselves – Study Finds Success With Natural Tooth Repair Method". SciTech Daily. Retrieved 27 June 2020.
  44. ^ "Japanese scientists grow teeth from single cells". Reuters. February 20, 2007. Retrieved 27 June 2020.
  45. ^ Normile, Dennis (August 3, 2009). "Researchers Grow New Teeth in Mice". Science.
  46. ^ Childs, Dan (April 13, 2009). "Could Baby Teeth Stem Cells Save Your Child?". ABC News. Retrieved 27 June 2020.
  47. ^ Ratan-NM, M. Pharm (April 30, 2020). "Repairing Teeth using Stem Cells". News Medical Life Sciences. Retrieved 27 June 2020.
  48. ^ Saldin, LT; Cramer, MC; Velankar, SS; White, LJ; Badylak, SF (February 2017). "Extracellular matrix hydrogels from decellularized tissues: Structure and function". Acta Biomaterialia. 49: 1–15. doi:10.1016/j.actbio.2016.11.068. PMC 5253110. PMID 27915024.
  49. ^ Swinehart, IT; Badylak, SF (March 2016). "Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis". Developmental Dynamics. 245 (3): 351–60. doi:10.1002/dvdy.24379. PMC 4755921. PMID 26699796.
  50. ^ Hannan, Daniel (October 25, 2020). "Taking back control of fishing could be an enormous growth opportunity for Britain". The Daily Telegraph.
  51. ^ a b "Fish Skin for Human Wounds: Iceland's Pioneering Treatment". Bloomberg Businessweek. 27 June 2017.
  52. ^ "Alaska's seafood industry by the numbers, plus fish skin's medical applications and antibiotics in Chilean salmon". Anchorage Daily News.
  53. ^ "FDA Approves Kerecis' Implantable Fish-Skin Product". Iceland Monitor.
  54. ^ a b Walther, Mary Margaret (2009). "Chapter 39. Cord Blood Hematopoietic Cell Transplantation". In Appelbaum, Frederick R.; Forman, Stephen J.; Negrin, Robert S.; Blume, Karl G. (eds.). Thomas' hematopoietic cell transplantation stem cell transplantation (4th ed.). Oxford: Wiley-Blackwell. ISBN 9781444303537.
  55. ^ a b Haller M J; et al. (2008). "Autologous umbilical cord blood infusion for type 1 diabetes". Exp. Hematol. 36 (6): 710–15. doi:10.1016/j.exphem.2008.01.009. PMC 2444031. PMID 18358588.
  56. ^ Caseiro, AR; Pereira, T; Ivanova, G; Luís, AL; Maurício, AC (2016). "Neuromuscular Regeneration: Perspective on the Application of Mesenchymal Stem Cells and Their Secretion Products". Stem Cells International. 2016: 9756973. doi:10.1155/2016/9756973. PMC 4736584. PMID 26880998.
  57. ^ Roura S, Pujal JM, Gálvez-Montón C, Bayes-Genis A (2015). "Impact of umbilical cord blood-derived mesenchymal stem cells on cardiovascular research". BioMed Research International. 2015: 975302. doi:10.1155/2015/975302. PMC 4377460. PMID 25861654.
  58. ^ Li, T; Xia, M; Gao, Y; Chen, Y; Xu, Y (2015). "Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy". Expert Opinion on Biological Therapy. 15 (9): 1293–306. doi:10.1517/14712598.2015.1051528. PMID 26067213. S2CID 25619787.
  59. ^ Hsueh, Ming-Feng; Önnerfjord, Patrik; Bolognesi, Michael P.; Easley, Mark E.; Kraus, Virginia B. (October 2019). "Analysis of "old" proteins unmasks dynamic gradient of cartilage turnover in human limbs". Science Advances. 5 (10): eaax3203. Bibcode:2019SciA....5R3203H. doi:10.1126/sciadv.aax3203. ISSN 2375-2548. PMC 6785252. PMID 31633025.
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Further reading edit

Non-technical further reading edit

  • Regenerative Medicine, gives more details about Regenerative Stem Cells.
  • Cogle CR; Guthrie SM; Sanders RC; Allen WL; Scott EW; Petersen BE (August 2003). "An overview of stem cell research and regulatory issues". Mayo Clinic Proceedings. 78 (8): 993–1003. doi:10.4065/78.8.993. PMID 12911047.
  • Kevin Strange and Viravuth Yin, "A Shot at Regeneration: A once abandoned drug compound shows an ability to rebuild organs damaged by illness and injury", Scientific American, vol. 320, no. 4 (April 2019), pp. 56–61.

Technical further reading edit

  • Metallo CM; Azarin SM; Ji L; de Pablo JJ; Palecek SP (June 2008). "Engineering tissue from human embryonic stem cells". Journal of Cellular and Molecular Medicine. 12 (3): 709–29. doi:10.1111/j.1582-4934.2008.00228.x. PMC 2670852. PMID 18194458.
  • Placzek, Mark R; Chung, I-Ming; Macedo, Hugo M; et al. (March 2009). "Stem cell bioprocessing: fundamentals and principles". Journal of the Royal Society Interface. 6 (32): 209–232. doi:10.1098/rsif.2008.0442. ISSN 1742-5689. PMC 2659585. PMID 19033137.

December 14, 2023
regenerative, medicine, deals, with, process, replacing, engineering, regenerating, human, animal, cells, tissues, organs, restore, establish, normal, function, this, field, holds, promise, engineering, damaged, tissues, organs, stimulating, body, repair, mech. Regenerative medicine deals with the process of replacing engineering or regenerating human or animal cells tissues or organs to restore or establish normal function 1 This field holds the promise of engineering damaged tissues and organs by stimulating the body s own repair mechanisms to functionally heal previously irreparable tissues or organs 2 A colony of human embryonic stem cellsRegenerative medicine also includes the possibility of growing tissues and organs in the laboratory and implanting them when the body cannot heal itself When the cell source for a regenerated organ is derived from the patient s own tissue or cells 3 the challenge of organ transplant rejection via immunological mismatch is circumvented 4 5 6 This approach could alleviate the problem of the shortage of organs available for donation Some of the biomedical approaches within the field of regenerative medicine may involve the use of stem cells 7 Examples include the injection of stem cells or progenitor cells obtained through directed differentiation cell therapies the induction of regeneration by biologically active molecules administered alone or as a secretion by infused cells immunomodulation therapy and transplantation of in vitro grown organs and tissues tissue engineering 8 9 Contents 1 History 2 Research 2 1 In dentistry 2 2 Extracellular matrix 2 3 Cord blood 3 See also 4 References 5 Further reading 5 1 Non technical further reading 5 2 Technical further readingHistory editThis section may rely excessively on sources too closely associated with the subject potentially preventing the article from being verifiable and neutral Please help improve it by replacing them with more appropriate citations to reliable independent third party sources October 2016 Learn how and when to remove this template message The ancient Greeks postulated whether parts of the body could be regenerated in the 700s BC 10 Skin grafting invented in the late 19th century can be thought of as the earliest major attempt to recreate bodily tissue to restore structure and function 11 Advances in transplanting body parts in the 20th century further pushed the theory that body parts could regenerate and grow new cells These advances led to tissue engineering and from this field the study of regenerative medicine expanded and began to take hold 10 This began with cellular therapy which led to the stem cell research that is widely being conducted today 12 The first cell therapies were intended to slow the aging process This began in the 1930s with Paul Niehans a Swiss doctor who was known to have treated famous historical figures such as Pope Pius XII Charlie Chaplin and king Ibn Saud of Saudi Arabia Niehans would inject cells of young animals usually lambs or calves into his patients in an attempt to rejuvenate them 13 14 In 1956 a more sophisticated process was created to treat leukemia by inserting bone marrow from a healthy person into a patient with leukemia This process worked mostly due to both the donor and receiver in this case being identical twins Nowadays bone marrow can be taken from people who are similar enough to the patient who needs the cells to prevent rejection 15 The term regenerative medicine was first used in a 1992 article on hospital administration by Leland Kaiser Kaiser s paper closes with a series of short paragraphs on future technologies that will impact hospitals One paragraph had Regenerative Medicine as a bold print title and stated A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems 16 17 The term was brought into the popular culture in 1999 by William A Haseltine when he coined the term during a conference on Lake Como to describe interventions that restore to normal function that which is damaged by disease injured by trauma or worn by time 18 Haseltine was briefed on the project to isolate human embryonic stem cells and embryonic germ cells at Geron Corporation in collaboration with researchers at the University of Wisconsin Madison and Johns Hopkins School of Medicine He recognized that these cells unique ability to differentiate into all the cell types of the human body pluripotency had the potential to develop into a new kind of regenerative therapy 19 20 Explaining the new class of therapies that such cells could enable he used the term regenerative medicine in the way that it is used today an approach to therapy that employs human genes proteins and cells to re grow restore or provide mechanical replacements for tissues that have been injured by trauma damaged by disease or worn by time and offers the prospect of curing diseases that cannot be treated effectively today including those related to aging 21 22 Later Haseltine would go on to explain that regenerative medicine acknowledges the reality that most people regardless of which illness they have or which treatment they require simply want to be restored to normal health Designed to be applied broadly the original definition includes cell and stem cell therapies gene therapy tissue engineering genomic medicine personalized medicine biomechanical prosthetics recombinant proteins and antibody treatments It also includes more familiar chemical pharmacopeia in short any intervention that restores a person to normal health In addition to functioning as shorthand for a wide range of technologies and treatments the term regenerative medicine is also patient friendly It solves the problem that confusing or intimidating language discourages patients The term regenerative medicine is increasingly conflated with research on stem cell therapies Some academic programs and departments retain the original broader definition while others use it to describe work on stem cell research 23 From 1995 to 1998 Michael D West PhD organized and managed the research between Geron Corporation and its academic collaborators James Thomson at the University of Wisconsin Madison and John Gearhart of Johns Hopkins University that led to the first isolation of human embryonic stem and human embryonic germ cells respectively 24 In March 2000 Haseltine Antony Atala M D Michael D West Ph D and other leading researchers founded E Biomed The Journal of Regenerative Medicine 25 The peer reviewed journal facilitated discourse around regenerative medicine by publishing innovative research on stem cell therapies gene therapies tissue engineering and biomechanical prosthetics The Society for Regenerative Medicine later renamed the Regenerative Medicine and Stem Cell Biology Society served a similar purpose creating a community of like minded experts from around the world 26 In June 2008 at the Hospital Clinic de Barcelona Professor Paolo Macchiarini and his team of the University of Barcelona performed the first tissue engineered trachea wind pipe transplantation Adult stem cells were extracted from the patient s bone marrow grown into a large population and matured into cartilage cells or chondrocytes using an adaptive method originally devised for treating osteoarthritis The team then seeded the newly grown chondrocytes as well as epithelial cells into a decellularised free of donor cells tracheal segment that was donated from a 51 year old transplant donor who had died of cerebral hemorrhage After four days of seeding the graft was used to replace the patient s left main bronchus After one month a biopsy elicited local bleeding indicating that the blood vessels had already grown back successfully 27 28 In 2009 the SENS Foundation was launched with its stated aim as the application of regenerative medicine defined to include the repair of living cells and extracellular material in situ to the diseases and disabilities of ageing 29 In 2012 Professor Paolo Macchiarini and his team improved upon the 2008 implant by transplanting a laboratory made trachea seeded with the patient s own cells 30 On September 12 2014 surgeons at the Institute of Biomedical Research and Innovation Hospital in Kobe Japan transplanted a 1 3 by 3 0 millimeter sheet of retinal pigment epithelium cells which were differentiated from iPS cells through directed differentiation into an eye of an elderly woman who suffers from age related macular degeneration 31 In 2016 Paolo Macchiarini was fired from Karolinska University in Sweden due to falsified test results and lies 32 The TV show Experimenten aired on Swedish Television and detailed all the lies and falsified results 33 Research editWidespread interest and funding for research on regenerative medicine has prompted institutions in the United States and around the world to establish departments and research institutes that specialize in regenerative medicine including The Department of Rehabilitation and Regenerative Medicine at Columbia University the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University the Center for Regenerative and Nanomedicine at Northwestern University the Wake Forest Institute for Regenerative Medicine and the British Heart Foundation Centers of Regenerative Medicine at the University of Oxford 34 35 36 37 In China institutes dedicated to regenerative medicine are run by the Chinese Academy of Sciences Tsinghua University and the Chinese University of Hong Kong among others 38 39 40 In dentistry edit nbsp A diagram of a human tooth Stem cells are located in the pulp in the center 41 Regenerative medicine has been studied by dentists to find ways that damaged teeth can be repaired and restored to obtain natural structure and function 42 Dental tissues are often damaged due to tooth decay and are often deemed to be irreplaceable except by synthetic or metal dental fillings or crowns which requires further damage to be done to the teeth by drilling into them to prevent the loss of an entire tooth Researchers from King s College London have created a drug called Tideglusib that claims to have the ability to regrow dentin the second layer of the tooth beneath the enamel which encases and protects the pulp often referred to as the nerve 43 Animal studies conducted on mice in Japan in 2007 show great possibilities in regenerating an entire tooth Some mice had a tooth extracted and the cells from bioengineered tooth germs were implanted into them and allowed to grow The result were perfectly functioning and healthy teeth complete with all three layers as well as roots These teeth also had the necessary ligaments to stay rooted in its socket and allow for natural shifting They contrast with traditional dental implants which are restricted to one spot as they are drilled into the jawbone 44 45 A person s baby teeth are known to contain stem cells that can be used for regeneration of the dental pulp after a root canal treatment or injury These cells can also be used to repair damage from periodontitis an advanced form of gum disease that causes bone loss and severe gum recession Research is still being done to see if these stem cells are viable enough to grow into completely new teeth Some parents even opt to keep their children s baby teeth in special storage with the thought that when older the children could use the stem cells within them to treat a condition 46 47 Extracellular matrix edit Extracellular matrix materials are commercially available and are used in reconstructive surgery treatment of chronic wounds and some orthopedic surgeries as of January 2017 clinical studies were under way to use them in heart surgery to try to repair damaged heart tissue 48 49 The use of fish skin with its natural constituent of omega 3 has been developed by an Icelandic company Kereceis 50 Omega 3 is a natural anti inflammatory and the fish skin material acts as a scaffold for cell regeneration 51 52 In 2016 their product Omega3 Wound was approved by the FDA for the treatment of chronic wounds and burns 51 In 2021 the FDA gave approval for Omega3 Surgibind to be used in surgical applications including plastic surgery 53 Cord blood edit Though uses of cord blood beyond blood and immunological disorders is speculative some research has been done in other areas 54 Any such potential beyond blood and immunological uses is limited by the fact that cord cells are hematopoietic stem cells which can differentiate only into blood cells and not pluripotent stem cells such as embryonic stem cells which can differentiate into any type of tissue Cord blood has been studied as a treatment for diabetes 55 However apart from blood disorders the use of cord blood for other diseases is not a routine clinical modality and remains a major challenge for the stem cell community 54 55 Along with cord blood Wharton s jelly and the cord lining have been explored as sources for mesenchymal stem cells MSC 56 and as of 2015 had been studied in vitro in animal models and in early stage clinical trials for cardiovascular diseases 57 as well as neurological deficits liver diseases immune system diseases diabetes lung injury kidney injury and leukemia 58 See also editAnti aging medicine Artificial organ Biomedicine LIN28 Osteoarthritis Research 59 60 Polyphyodont Regeneration in humans Regenerative endodontics Rejuvenation aging Stem cell treatments TERMIS Tooth regenerationReferences edit Mason Chris Dunnill Peter 2008 A brief definition of regenerative medicine Regenerative Medicine 3 1 1 5 doi 10 2217 17460751 3 1 1 ISSN 1746 0751 PMID 18154457 UM Leads in the Field of Regenerative Medicine Moving from Treatments to Cures Healthcanal com 8 May 2014 Mahla RS 2016 Stem cells application in regenerative medicine and disease threpeutics International Journal of Cell Biology 2016 7 1 24 doi 10 1155 2016 6940283 PMC 4969512 PMID 27516776 Regenerative Medicine NIH Fact sheet PDF September 2006 Archived from the original PDF on 2011 10 26 Retrieved 2010 08 16 Mason C Dunnill P January 2008 A brief definition of regenerative medicine Regenerative Medicine 3 1 1 5 doi 10 2217 17460751 3 1 1 PMID 18154457 Regenerative medicine glossary Regenerative Medicine 4 4 Suppl S1 88 July 2009 doi 10 2217 rme 09 s1 PMID 19604041 Riazi AM Kwon SY Stanford WL 2009 Stem Cell Sources for Regenerative Medicine Stem Cells in Regenerative Medicine Methods in Molecular Biology Vol 482 pp 55 90 doi 10 1007 978 1 59745 060 7 5 ISBN 978 1 58829 797 6 PMID 19089350 Stoick Cooper CL Moon RT Weidinger G June 2007 Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine Genes amp Development 21 11 1292 315 doi 10 1101 gad 1540507 PMID 17545465 Muneoka K Allan CH Yang X Lee J Han M December 2008 Mammalian regeneration and regenerative medicine Birth Defects Research Part C Embryo Today 84 4 265 80 doi 10 1002 bdrc 20137 PMID 19067422 a b What is Regenerative Medicine University of Nebraska Medical Center University of Nebraska Retrieved 27 June 2020 Rahlf Sidsel Hald 2009 The Use of Skin Grafting for the Treatment of Burn Wounds in Denmark 1870 1960 Dansk Medicinhistorisk Arbog 37 99 116 PMID 20509454 Retrieved June 27 2020 Sampogna Gianluca Guraya Salman Yousuf Forgione Atonello September 2015 Regenerative medicine Historical roots and potential strategies in modern medicine Journal of Microscopy and Ultrastructure 3 3 101 107 doi 10 1016 j jmau 2015 05 002 PMC 6014277 PMID 30023189 Dr Paul Niehans Swiss Surgeon 89 The New York Times September 4 1971 Retrieved 27 June 2020 Dr Paul Niehans was a former physician of Pope Paul XII among others A surgeon who performed more than 50 000 operations in 40 years he developed his own rejuvenation treatment by injecting humans with the foetus of unborn lambs and other animals Milton Joyce 1998 Tramp The Life of Charlie Chaplin HarperCollins ISBN 0060170522 1956 The First Successful Bone Marrow Transplantation Home cancerresearch 7 December 2014 Archived from the original on 2 February 2020 Retrieved 26 July 2020 Kaiser LR 1992 The future of multihospital systems Topics in Health Care Financing 18 4 32 45 PMID 1631884 Lysaght MJ Crager J July 2009 Origins Tissue Engineering Part A 15 7 1449 50 doi 10 1089 ten tea 2007 0412 PMID 19327019 https www nsf gov pubs 2004 nsf0450 Viola J Lal B and Grad O The Emergence of Tissue Engineering as a Research Field Arlington VA National Science Foundation 2003 Bailey Ron 2005 Liberation Biology The Scientific and Moral Case for the Biotech Revolution Prometheus Books Alexander Brian January 2000 Don t Die Stay Pretty The exploding science of superlongevity Wired Vol 8 no 1 Haseltine WA 6 July 2004 The Emergence of Regenerative Medicine A New Field and a New Society E biomed The Journal of Regenerative Medicine 2 4 17 23 doi 10 1089 152489001753309652 Mao AS Mooney DJ Nov 2015 Regenerative medicine Current therapies and future directions Proc Natl Acad Sci U S A 112 47 14452 9 Bibcode 2015PNAS 11214452M doi 10 1073 pnas 1508520112 PMC 4664309 PMID 26598661 Sampogna Gianluca Guraya Salman Yousuf Forgione Antonello 2015 09 01 Regenerative medicine Historical roots and potential strategies in modern medicine Journal of Microscopy and Ultrastructure 3 3 101 107 doi 10 1016 j jmau 2015 05 002 ISSN 2213 879X PMC 6014277 PMID 30023189 Bloomberg Longevity Economy Conference 2013 Panelist Bio Archived from the original on 2013 08 03 E Biomed The Journal of Regenerative Medicine E Biomed ISSN 1524 8909 Retrieved 2020 02 25 Haseltine William A 2011 07 01 Interview Commercial translation of cell based therapies and regenerative medicine learning by experience Regenerative Medicine 6 4 431 435 doi 10 2217 rme 11 40 ISSN 1746 0751 PMID 21749201 Tissue Engineered Trachea Transplant Is Adult Stem Cell Breakthrough Science 2 0 2008 11 19 Retrieved 2010 03 19 Regenerative Medicine Success Story A Tissue Engineered Trachea Mirm pitt edu Archived from the original on 2010 06 12 Retrieved 2010 03 19 Sens Foundation sens org 2009 01 03 Retrieved 2012 02 23 Fountain Henry 2012 01 12 Surgeons Implant Synthetic Trachea In Baltimore Man The New York Times Retrieved 2012 02 23 Cyranoski David 12 September 2014 Japanese woman is first recipient of next generation stem cells Nature doi 10 1038 nature 2014 15915 ISSN 0028 0836 S2CID 86969754 Oltermann Philip 2016 03 24 Superstar doctor fired from Swedish institute over research lies The Guardian ISSN 0261 3077 Retrieved 2017 10 13 Sweden Sveriges Television AB Stockholm Experimenten svt se in Swedish Retrieved 2017 10 13 a href Template Cite web html title Template Cite web cite web a CS1 maint multiple names authors list link Research Institute for Stem Cell Biologyand Regenerative Medicine Retrieved 2020 02 25 CRN Origins and Mission Center for Regenerative Nanomedicine Northwestern University crn northwestern edu Retrieved 2020 02 25 Wake Forest Institute for Regenerative Medicine WFIRM Wake Forest School of Medicine Retrieved 2020 02 25 Centres of Regenerative Medicine www bhf org uk Retrieved 2020 02 25 Guangzhou Institute of Biomedicine and Health Chinese Academy of Sciences english gibh cas cn Retrieved 2020 02 25 Institute for Stem Cell Biology and Regenerative Medicine School of Pharmaceutical Sciences Tsinghua University www sps tsinghua edu cn Archived from the original on 2016 10 04 Retrieved 2020 02 25 administrator Home Institute for Tissue Engineering and Regenerative Medicine Retrieved 2020 02 25 Lan Xiaoyan Sun Zhengwu Chu Chengyan Boltze Johannes Li Shen 2 August 2019 Dental Pulp Stem Cells An Attractive Alternative for Cell Therapy in Ischemic Stroke Frontiers in Neurology 10 824 doi 10 3389 fneur 2019 00824 PMC 6689980 PMID 31428038 S2CID 199022265 Steindorff Marina M Lehl Helena Winkel Andreas Stiesch Meike February 2014 Innovative approaches to regenerate teeth by tissue engineering Archives of Oral Biology 59 2 158 66 doi 10 1016 j archoralbio 2013 11 005 PMID 24370187 Retrieved 27 June 2020 King s College London March 10 2020 Teeth That Repair Themselves Study Finds Success With Natural Tooth Repair Method SciTech Daily Retrieved 27 June 2020 Japanese scientists grow teeth from single cells Reuters February 20 2007 Retrieved 27 June 2020 Normile Dennis August 3 2009 Researchers Grow New Teeth in Mice Science Childs Dan April 13 2009 Could Baby Teeth Stem Cells Save Your Child ABC News Retrieved 27 June 2020 Ratan NM M Pharm April 30 2020 Repairing Teeth using Stem Cells News Medical Life Sciences Retrieved 27 June 2020 Saldin LT Cramer MC Velankar SS White LJ Badylak SF February 2017 Extracellular matrix hydrogels from decellularized tissues Structure and function Acta Biomaterialia 49 1 15 doi 10 1016 j actbio 2016 11 068 PMC 5253110 PMID 27915024 Swinehart IT Badylak SF March 2016 Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis Developmental Dynamics 245 3 351 60 doi 10 1002 dvdy 24379 PMC 4755921 PMID 26699796 Hannan Daniel October 25 2020 Taking back control of fishing could be an enormous growth opportunity for Britain The Daily Telegraph a b Fish Skin for Human Wounds Iceland s Pioneering Treatment Bloomberg Businessweek 27 June 2017 Alaska s seafood industry by the numbers plus fish skin s medical applications and antibiotics in Chilean salmon Anchorage Daily News FDA Approves Kerecis Implantable Fish Skin Product Iceland Monitor a b Walther Mary Margaret 2009 Chapter 39 Cord Blood Hematopoietic Cell Transplantation In Appelbaum Frederick R Forman Stephen J Negrin Robert S Blume Karl G eds Thomas hematopoietic cell transplantation stem cell transplantation 4th ed Oxford Wiley Blackwell ISBN 9781444303537 a b Haller M J et al 2008 Autologous umbilical cord blood infusion for type 1 diabetes Exp Hematol 36 6 710 15 doi 10 1016 j exphem 2008 01 009 PMC 2444031 PMID 18358588 Caseiro AR Pereira T Ivanova G Luis AL Mauricio AC 2016 Neuromuscular Regeneration Perspective on the Application of Mesenchymal Stem Cells and Their Secretion Products Stem Cells International 2016 9756973 doi 10 1155 2016 9756973 PMC 4736584 PMID 26880998 Roura S Pujal JM Galvez Monton C Bayes Genis A 2015 Impact of umbilical cord blood derived mesenchymal stem cells on cardiovascular research BioMed Research International 2015 975302 doi 10 1155 2015 975302 PMC 4377460 PMID 25861654 Li T Xia M Gao Y Chen Y Xu Y 2015 Human umbilical cord mesenchymal stem cells an overview of their potential in cell based therapy Expert Opinion on Biological Therapy 15 9 1293 306 doi 10 1517 14712598 2015 1051528 PMID 26067213 S2CID 25619787 Hsueh Ming Feng Onnerfjord Patrik Bolognesi Michael P Easley Mark E Kraus Virginia B October 2019 Analysis of old proteins unmasks dynamic gradient of cartilage turnover in human limbs Science Advances 5 10 eaax3203 Bibcode 2019SciA 5R3203H doi 10 1126 sciadv aax3203 ISSN 2375 2548 PMC 6785252 PMID 31633025 Humans Have Salamander Like Ability to Regrow Cartilage in Joints Duke Health October 8 2019 Further reading editNon technical further reading edit Regenerative Medicine gives more details about Regenerative Stem Cells Cogle CR Guthrie SM Sanders RC Allen WL Scott EW Petersen BE August 2003 An overview of stem cell research and regulatory issues Mayo Clinic Proceedings 78 8 993 1003 doi 10 4065 78 8 993 PMID 12911047 Kevin Strange and Viravuth Yin A Shot at Regeneration A once abandoned drug compound shows an ability to rebuild organs damaged by illness and injury Scientific American vol 320 no 4 April 2019 pp 56 61 Technical further reading edit Metallo CM Azarin SM Ji L de Pablo JJ Palecek SP June 2008 Engineering tissue from human embryonic stem cells Journal of Cellular and Molecular Medicine 12 3 709 29 doi 10 1111 j 1582 4934 2008 00228 x PMC 2670852 PMID 18194458 Placzek Mark R Chung I Ming Macedo Hugo M et al March 2009 Stem cell bioprocessing fundamentals and principles Journal of the Royal Society Interface 6 32 209 232 doi 10 1098 rsif 2008 0442 ISSN 1742 5689 PMC 2659585 PMID 19033137 Retrieved from https en wikipedia org w index php title Regenerative medicine amp oldid 1189520315, 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