Regenerative medicine is a branch of translational research in tissue engineering and molecular biology which deals with the "process of replacing, engineering or regenerating human or animal cells, tissues or organs to restore or establish normal function". 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.
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, the challenge of organ transplant rejection via immunological mismatch is circumvented. 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. 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).
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."
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. 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. 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".
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 of confusing or intimidating language discourage to 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.
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.
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. 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.
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.
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". 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.
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.
In 2016, Paolo Macchiarini was fired from Karolinska University in Sweden due to falsified test results and lies. The TV-show Experimenten aired on Swedish Television and detailed all the lies and falsified results.
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. 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.
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.
Though uses of cord blood beyond blood and immunological disorders is speculative, some research has been done in other areas. 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. 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.
Along with cord blood, Wharton's jelly and the cord lining have been explored as sources for mesenchymal stem cells (MSC), and as of 2015 had been studied in vitro, in animal models, and in early stage clinical trials for cardiovascular diseases, as well as neurological deficits, liver diseases, immune system diseases, diabetes, lung injury, kidney injury, and leukemia.
- "New health facility aims to translate stem cell science into therapies". 2014-05-09.
- Mason, Chris; Dunnill, Peter (2008). "A brief definition of regenerative medicine". Regenerative Medicine. 3 (1): 1–5. doi:10.2217/174607184.108.40.206. 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.CS1 maint: uses authors parameter (link)
- "Regenerative Medicine. NIH Fact sheet" (PDF). September 2006. Retrieved 2010-08-16.
- Mason C; Dunnill P (January 2008). "A brief definition of regenerative medicine". Regenerative Medicine. 3 (1): 1–5. doi:10.2217/174607220.127.116.11. 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. Methods in Molecular Biology. 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 & 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.
- 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. "Don't Die, Stay Pretty: The exploding science of superlongevity". Wired.
- 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. 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 (JournalSeek)". journalseek.net. 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". Scientificblogging.com. 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.
- "Surgeons Implant Synthetic Trachea In Baltimore Man". nytimes.com. 2012-01-12. Retrieved 2012-02-23.
- "Next-Generation Stem Cells Transplanted in Human for the First Time". Nature. Retrieved 2014-09-12.
- 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.
- "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. Retrieved 2020-02-25.
- administrator. "Home". Institute for Tissue Engineering and Regenerative Medicine. Retrieved 2020-02-25.
- 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.
- 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.
- 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; 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.
- 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.
- 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.
- Analysis of “old” proteins unmasks dynamic gradient of cartilage turnover in human limbs
- Humans Have Salamander-Like Ability to Regrow Cartilage in Joints
Non-technical further reading
- 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
- 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 MR, Chung IM, Macedo HM, et al. (March 2009). "Stem cell bioprocessing: fundamentals and principles". Journal of the Royal Society, Interface. 6 (32): 209–32. doi:10.1098/rsif.2008.0442. PMC 2659585. PMID 19033137.