Regenerative medicine

Short description: Medical field involved in regenerating tissues

A colony of human embryonic stem cells

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]

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]

## Contents

* 1 History
* 2 Research
* 2.1 In dentistry
* 2.2 Extracellular matrix
* 2.3 Cord blood
* 2.4 Bioelectricity
* 3 See also
* 4 References
* 5 Further reading

## History

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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

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

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

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

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]

### Bioelectricity

The potential use of developmental bioelectricity in regenerative medicine is under active investigation, with particular interest in future organ and limb regeneration guided by bioelectric stimulation.[59] Developmental bioelectricity refers to endogenous ion flows and voltage gradients across cell membranes (Vmem) in excitable (able to create an action potential) and non-excitable tissues that provide instructive cues for growth. These bioelectric states, set by ion channels and pumps, are propagated through gap-junction coupling and together with chemical gradients and physical forces they form long-range patterning circuits. Through voltage-sensitive signalling pathways, changes in Vmem modulate gene expression and cell behaviours (proliferation, migration, differentiation), thereby shaping tissue growth and polarity.[60]

Experiments in vertebrate and invertebrate models indicate that bioelectric cues can steer regeneration. In Xenopus tadpoles, activating a proton pump (V-ATPase) that moves hydrogen ions out of cells is necessary for tail regrowth and can restore regeneration during a normally refractory stage; in adult Zebrafish, inhibiting the same pump impairs fin regrowth.[61][62] In Planarians, brief electrical perturbations can cause tail pieces to form heads (including two-headed animals) or to regenerate heads resembling other species.[63][64] In adult frogs, a 24-hour treatment with a drug-delivering ‘BioDome’ device initiated long-term hindlimb regrowth with multi-tissue repair and functional recovery.[65]

Proposed techniques combine pharmacological control of ion channels and gap junctions, optogenetic actuators to write Vmem patterns with light, and devices that condition the injury microenvironment or apply controlled direct-current fields.[66] Proposed tools include voltage-sensitive dyes, microelectrodes, and wearable or implantable stimulators.[67][65] Some researchers and commentators note that, despite encouraging animal studies, evidence for large-scale appendage or organ regrowth in mammals remains limited, and achieving it will require standardized outcome measures, reproducible protocols across models, and safe, precise methods to control tissue electrical states in the body.[68][69][70]

## See also

* Artificial organ
* Regenerative biology
* Biomedicine
* Cloning
* Induced pluripotent stem cell
* Life extension
* LIN28
* Neuroregeneration
* Orthobiologics
* Osteoarthritis[71][72]
* Polyphyodont
* Regeneration in humans
* Regenerative endodontics
* Rejuvenation (aging)
* RepliCel, Canadian regenerative medicine company
* SPIONs
* Stem cell treatments
* TERMIS
* Tooth regeneration

## References

1. ↑ "A brief definition of regenerative medicine" (in en). Regenerative Medicine 3 (1): 1–5. 2008. 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. http://www.healthcanal.com/public-health-safety/50621-um-leads-in-the-field-of-regenerative-medicine-moving-from-treatments-to-cures.html.
3. ↑ "Stem cells application in regenerative medicine and disease threpeutics". International Journal of Cell Biology 2016 (7). 2016. doi:10.1155/2016/6940283. PMID 27516776.
4. ↑ "Regenerative Medicine. NIH Fact sheet". September 2006. https://report.nih.gov/nihfactsheets/Pdfs/RegenerativeMedicine(NIBIB).pdf.
5. ↑ "A brief definition of regenerative medicine". Regenerative Medicine 3 (1): 1–5. January 2008. 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. ↑ "Stem Cell Sources for Regenerative Medicine". Stem Cells in Regenerative Medicine. Methods in Molecular Biology. 482. 2009. pp. 55–90. doi:10.1007/978-1-59745-060-7_5. ISBN 978-1-58829-797-6.
8. ↑ "Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine". Genes & Development 21 (11): 1292–1315. June 2007. doi:10.1101/gad.1540507. PMID 17545465.
9. ↑ "Mammalian regeneration and regenerative medicine". Birth Defects Research. Part C, Embryo Today 84 (4): 265–280. December 2008. doi:10.1002/bdrc.20137. PMID 19067422.
10. ↑ 10.0 10.1 "What is Regenerative Medicine?". University of Nebraska. https://www.unmc.edu/regenerativemed/about/whatis/index.html.
11. ↑ "The Use of Skin Grafting for the Treatment of Burn Wounds in Denmark 1870-1960". Dansk Medicinhistorisk Arbog 37: 99–116. 2009. PMID 20509454.
12. ↑ "Regenerative medicine: Historical roots and potential strategies in modern medicine". Journal of Microscopy and Ultrastructure 3 (3): 101–107. September 2015. doi:10.1016/j.jmau.2015.05.002. PMID 30023189.
13. ↑ "Dr. Paul Niehans, Swiss Surgeon, 89". The New York Times. September 4, 1971. https://www.nytimes.com/1971/09/04/archives/dr-paul-niehans-swiss-surgeon-89-expert-in-cellular-therapy-against.html. "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. ↑ Tramp: The Life of Charlie Chaplin. HarperCollins. 1998. ISBN 978-0-06-017052-3.
15. ↑ "1956: The First Successful Bone Marrow Transplantation". Home.cancerresearch. 7 December 2014. https://home.cancerresearch/1956-the-first-successful-bone-marrow-transplantation/.
16. ↑ "The future of multihospital systems". Topics in Health Care Financing 18 (4): 32–45. 1992. PMID 1631884.
17. ↑ "Origins". Tissue Engineering. Part A 15 (7): 1449–1450. July 2009. 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.
19. ↑ Liberation Biology: The Scientific and Moral Case for the Biotech Revolution. Prometheus Books. 2005.
20. ↑ "Don't Die, Stay Pretty: The exploding science of superlongevity". Wired 8 (1). January 2000. https://www.wired.com/2000/01/forever/.
21. ↑ "The Emergence of Regenerative Medicine: A New Field and a New Society". E-biomed: The Journal of Regenerative Medicine 2 (4): 17–23. 6 July 2004. doi:10.1089/152489001753309652.
22. ↑ "Regenerative medicine: Current therapies and future directions". Proc Natl Acad Sci U S A 112 (47): 14452–14459. Nov 2015. doi:10.1073/pnas.1508520112. PMID 26598661. Bibcode: 2015PNAS..11214452M.
23. ↑ "Regenerative medicine: Historical roots and potential strategies in modern medicine" (in en). Journal of Microscopy and Ultrastructure 3 (3): 101–107. 2015-09-01. doi:10.1016/j.jmau.2015.05.002. ISSN 2213-879X. PMID 30023189.
24. ↑ "Bloomberg Longevity Economy Conference 2013 Panelist Bio". http://www.bloomberglink.com/people/michael-d-west-ph-d/.
25. ↑ "E-Biomed: The Journal of Regenerative Medicine". E-Biomed. ISSN 1524-8909. http://journalseek.net/cgi-bin/journalseek/journalsearch.cgi?field=issn&query=1524-8909. Retrieved 2020-02-25.
26. ↑ "Interview: Commercial translation of cell-based therapies and regenerative medicine: learning by experience". Regenerative Medicine 6 (4): 431–435. 2011-07-01. 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. http://www.scientificblogging.com/news_releases/tissueengineered_trachea_transplant_adult_stem_cell_breakthrough.
28. ↑ "Regenerative Medicine Success Story: A Tissue-Engineered Trachea". Mirm.pitt.edu. http://www.mirm.pitt.edu/news/article.asp?qEmpID=395.
29. ↑ "Sens Foundation". sens.org. 2009-01-03. http://www.sens.org?ref=health.
30. ↑ "Surgeons Implant Synthetic Trachea In Baltimore Man". The New York Times. 2012-01-12. https://www.nytimes.com/2012/01/13/health/research/surgeons-transplant-synthetic-trachea-in-baltimore-man.html.
31. ↑ "Japanese woman is first recipient of next-generation stem cells". Nature. 12 September 2014. doi:10.1038/nature.2014.15915. ISSN 0028-0836.
32. ↑ "'Superstar doctor' fired from Swedish institute over research 'lies'" (in en-GB). The Guardian. 2016-03-24. ISSN 0261-3077. https://www.theguardian.com/science/2016/mar/23/superstar-doctor-fired-from-swedish-institute-over-research-lies-allegations-windpipe-surgery.
33. ↑ "Experimenten" (in sv). https://www.svt.se/dokument-inifran-experimenten/.
34. ↑ "Research" (in en). http://med.stanford.edu/stemcell/research.html.
35. ↑ "CRN Origins and Mission | Center for Regenerative Nanomedicine, Northwestern University". http://crn.northwestern.edu/about-crn.
36. ↑ "Wake Forest Institute for Regenerative Medicine (WFIRM)". https://school.wakehealth.edu/Research/Institutes-and-Centers/Wake-Forest-Institute-for-Regenerative-Medicine.
37. ↑ "Centres of Regenerative Medicine" (in en). https://www.bhf.org.uk/what-we-do/our-research/mending-broken-hearts/research/centres-of-regenerative-medicine.
38. ↑ "Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences". http://english.gibh.cas.cn/sci/overview/.
39. ↑ "Institute for Stem Cell Biology and Regenerative Medicine - School of Pharmaceutical Sciences Tsinghua University". http://www.sps.tsinghua.edu.cn/en/study/ganxibao.html.
40. ↑ administrator. "Home" (in en-US). https://www.iterm.cuhk.edu.hk/.
41. ↑ "Dental Pulp Stem Cells: An Attractive Alternative for Cell Therapy in Ischemic Stroke". Frontiers in Neurology 10. 2 August 2019. doi:10.3389/fneur.2019.00824. PMID 31428038.
42. ↑ "Innovative approaches to regenerate teeth by tissue engineering". Archives of Oral Biology 59 (2): 158–166. February 2014. doi:10.1016/j.archoralbio.2013.11.005. PMID 24370187. https://www.sciencedirect.com/science/article/abs/pii/S0003996913003427. Retrieved 27 June 2020.
43. ↑ King's College London (March 10, 2020). "Teeth That Repair Themselves – Study Finds Success With Natural Tooth Repair Method". https://scitechdaily.com/teeth-that-repair-themselves-study-finds-success-with-natural-tooth-repair-method/.
44. ↑ "Japanese scientists grow teeth from single cells". Reuters. February 20, 2007. https://www.reuters.com/article/us-teeth-mice/japanese-scientists-grow-teeth-from-single-cells-idUSN1834654020070220#:~:text=WASHINGTON (Reuters) - Japanese researchers,and transplanted them into mice..
45. ↑ "Researchers Grow New Teeth in Mice". Science. August 3, 2009. https://www.science.org/content/article/researchers-grow-new-teeth-mice.
46. ↑ "Could Baby Teeth Stem Cells Save Your Child?". ABC News. April 13, 2009. https://abcnews.go.com/Health/Dental/story?id=4942116&page=1.
47. ↑ "Repairing Teeth using Stem Cells". April 30, 2020. https://www.news-medical.net/health/Repairing-Teeth-using-Stem-Cells.aspx.
48. ↑ "Extracellular matrix hydrogels from decellularized tissues: Structure and function.". Acta Biomaterialia 49: 1–15. February 2017. doi:10.1016/j.actbio.2016.11.068. PMID 27915024.
49. ↑ "Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis.". Developmental Dynamics 245 (3): 351–360. March 2016. doi:10.1002/dvdy.24379. PMID 26699796.
50. ↑ "Taking back control of fishing could be an enormous growth opportunity for Britain". October 25, 2020. https://www.telegraph.co.uk/news/2020/10/25/taking-back-control-fishing-could-enormous-growth-opportunity/.
51. ↑ 51.0 51.1 "Fish Skin for Human Wounds: Iceland's Pioneering Treatment". 27 June 2017. https://www.bloomberg.com/news/features/2017-06-27/fish-skin-may-be-the-answer-to-chronic-wounds.
52. ↑ "Alaska's seafood industry by the numbers, plus fish skin's medical applications and antibiotics in Chilean salmon". https://www.adn.com/business-economy/2019/04/30/alaskas-seafood-industry-by-the-numbers-plus-fish-skins-medical-applications-and-antibiotics-in-chilean-salmon/.
53. ↑ "FDA Approves Kerecis' Implantable Fish-Skin Product". https://icelandmonitor.mbl.is/news/news/2021/10/22/fda_approves_kerecis_implantable_fish_skin_product/.
54. ↑ 54.0 54.1 "Chapter 39. Cord Blood Hematopoietic Cell Transplantation". Thomas' hematopoietic cell transplantation stem cell transplantation (4th ed.). Oxford: Wiley-Blackwell. 2009. ISBN 978-1-4443-0353-7.
55. ↑ 55.0 55.1 "Autologous umbilical cord blood infusion for type 1 diabetes". Exp. Hematol. 36 (6): 710–715. Jun 2008. doi:10.1016/j.exphem.2008.01.009. PMID 18358588.
56. ↑ "Neuromuscular Regeneration: Perspective on the Application of Mesenchymal Stem Cells and Their Secretion Products.". Stem Cells International 2016. 2016. doi:10.1155/2016/9756973. PMID 26880998.
57. ↑ "Impact of umbilical cord blood-derived mesenchymal stem cells on cardiovascular research". BioMed Research International 2015. 2015. doi:10.1155/2015/975302. PMID 25861654.
58. ↑ "Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy.". Expert Opinion on Biological Therapy 15 (9): 1293–1306. 2015. doi:10.1517/14712598.2015.1051528. PMID 26067213.
59. ↑ "Endogenous Bioelectrics in Development, Cancer, and Regeneration: Drugs and Bioelectronic Devices as Electroceuticals for Regenerative Medicine". iScience 22: 519–533. 20 December 2019. doi:10.1016/j.isci.2019.11.023. ISSN 2589-0042. PMID 31837520. Bibcode: 2019iSci...22..519L.
60. ↑ "Molecular bioelectricity: how endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo". Molecular Biology of the Cell 25 (24): 3835–3850. December 2014. doi:10.1091/mbc.e13-12-0708. PMID 25425556.
61. ↑ "Electric currents in Xenopus tadpole tail regeneration". Developmental Biology 335 (1): 198–207. 1 November 2009. doi:10.1016/j.ydbio.2009.08.028. ISSN 0012-1606. PMID 19733557. https://www.sciencedirect.com/science/article/pii/S0012160609011683.
62. ↑ "V-ATPase proton pumping activity is required for adult zebrafish appendage regeneration.". PLOS ONE 9 (3). 2014. doi:10.1371/journal.pone.0092594. PMID 24671205. Bibcode: 2014PLoSO...992594M.
63. ↑ "A Chemical Genetics Approach Reveals H,K-ATPase-Mediated Membrane Voltage Is Required for Planarian Head Regeneration". Chemistry & Biology 18 (1): 77–89. January 2011. doi:10.1016/j.chembiol.2010.11.012. PMID 21276941.
64. ↑ "Gap Junctional Blockade Stochastically Induces Different Species-Specific Head Anatomies in Genetically Wild-Type Girardia dorotocephala Flatworms". International Journal of Molecular Sciences 16 (11): 27865–27896. 24 November 2015. doi:10.3390/ijms161126065. PMID 26610482.
65. ↑ 65.0 65.1 "Acute multidrug delivery via a wearable bioreactor facilitates long-term limb regeneration and functional recovery in adult Xenopus laevis". Science Advances 8 (4). 28 January 2022. doi:10.1126/sciadv.abj2164. PMID 35080969. Bibcode: 2022SciA....8.2164M.
66. ↑ "Endogenous Bioelectrics in Development, Cancer, and Regeneration: Drugs and Bioelectronic Devices as Electroceuticals for Regenerative Medicine". iScience 22: 519–533. December 2019. doi:10.1016/j.isci.2019.11.023. PMID 31837520. Bibcode: 2019iSci...22..519L.
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68. ↑ "Making Sense of Electrical Stimulation: A Meta-analysis for Wound Healing". Annals of Biomedical Engineering 52 (2): 153–177. February 2024. doi:10.1007/s10439-023-03371-2. PMID 37743460.
69. ↑ "Inducing Vertebrate Limb Regeneration: A Review of Past Advances and Future Outlook.". Cold Spring Harbor Perspectives in Biology 14 (4). 17 May 2022. doi:10.1101/cshperspect.a040782. PMID 34400551.
70. ↑ "Generation of direct current electrical fields as regenerative therapy for spinal cord injury: A review". APL Bioengineering 7 (3). 1 September 2023. doi:10.1063/5.0152669. PMID 37736015.
71. ↑ "Analysis of "old" proteins unmasks dynamic gradient of cartilage turnover in human limbs". Science Advances 5 (10). October 2019. doi:10.1126/sciadv.aax3203. ISSN 2375-2548. PMID 31633025. Bibcode: 2019SciA....5R3203H.
72. ↑ "Humans Have Salamander-Like Ability to Regrow Cartilage in Joints". Duke Health. October 8, 2019. https://corporate.dukehealth.org/news-listing/humans-have-salamander-ability-regrow-cartilage-joints.

## Further reading

* "Regenerative Medicine – Cellular Medicine". Adigos Stem Cells. http://www.adigosstemcells.com/regenerative-medicines.php.
* "An overview of stem cell research and regulatory issues". Mayo Clinic Proceedings 78 (8): 993–1003. August 2003. doi:10.4065/78.8.993. PMID 12911047.
* "A Shot at Regeneration: A once abandoned drug compound shows an ability to rebuild organs damaged by illness and injury". Scientific American 320 (4): 56–61. April 2019. doi:10.1038/scientificamerican0419-56. PMID 39010484.
* "Engineering tissue from human embryonic stem cells". Journal of Cellular and Molecular Medicine 12 (3): 709–729. June 2008. doi:10.1111/j.1582-4934.2008.00228.x. PMID 18194458.
* "Stem cell bioprocessing: fundamentals and principles". Journal of the Royal Society Interface 6 (32): 209–232. March 2009. doi:10.1098/rsif.2008.0442. ISSN 1742-5689. PMID 19033137.

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* Pediatric surgery
* Plastic surgery
* Reproductive surgery
* Surgical oncology
* Thoracic surgery
* Transplant surgery
* Trauma surgery
* Urology
* Andrology
* Vascular surgery

Internal medicine

* Allergy / Immunology
* Angiology
* Cardiology
* Endocrinology
* Gastroenterology
* Hepatology
* Geriatrics
* Hematology
* Hospital medicine|
* Infectious disease
* Nephrology
* Oncology
* Pulmonology
* Rheumatology

Obstetrics and gynaecology

* Gynaecology
* Gynecologic oncology
* Maternal–fetal medicine
* Obstetrics
* Reproductive endocrinology and infertility
* Urogynecology

Diagnostic

* Radiology
* Interventional radiology
* Nuclear medicine
* Pathology
* Anatomical
* Clinical pathology
* Clinical chemistry
* Clinical immunology
* Cytopathology
* Medical microbiology
* Transfusion medicine

Other specialties

* Addiction medicine
* Adolescent medicine
* Anesthesiology
* Dermatology
* Disaster medicine
* Diving medicine
* Emergency medicine
* Mass gathering medicine
* Family medicine
* General practice
* Hospital medicine
* Intensive care medicine
* Medical genetics
* Narcology
* Neurology
* Clinical neurophysiology
* Occupational medicine
* Ophthalmology
* Oral medicine
* Pain management
* Palliative care
* Pediatrics
* Neonatology
* Physical medicine and rehabilitation
* PM&R
* Preventive medicine
* Psychiatry
* Addiction psychiatry
* Radiation oncology
* Reproductive medicine
* Sexual medicine
* Sleep medicine
* Sports medicine
* Transplantation medicine
* Tropical medicine
* Travel medicine
* Venereology

Medical education|

* Medical school
* Bachelor of Medicine, Bachelor of Surgery
* Bachelor of Medical Sciences
* Master of Medicine
* Master of Surgery
* Doctor of Medicine
* Doctor of Osteopathic Medicine
* MD–PhD

Related topics|

* Alternative medicine
* Allied health
* Dentistry
* Podiatry
* Physiotherapy
* Molecular oncology
* Nanomedicine
* Personalized medicine
* Public health
* Traditional medicine
* Veterinary medicine
* Physician
* Chief physician
* History of medicine

* Book
* Category
* Commons
* Wikiproject
* Portal
* Outline

* v
* t
* e

Emerging technologies

Fields|

| Agriculture|

* Agricultural robot
* Cellular agriculture
* Closed ecological systems
* Cultured meat
* Genetically modified food
* Precision agriculture
* Vertical farming

|

Architecture|

* Arcology
* Building printing
* Contour crafting
* Domed city

Biomedical|

* Artificial uterus
* Ampakine
* Brain transplant
* Cryonics
* Cryoprotectant
* Cryopreservation
* Vitrification
* Suspended animation
* De-extinction
* Genetic engineering
* Gene therapy
* Head transplant
* Isolated brain
* Life extension
* Strategies for Engineered Negligible Senescence
* Nanomedicine
* Nanosensors
* Organ printing
* Personalized medicine
* Regenerative medicine
* Stem-cell therapy
* Tissue engineering
* Robot-assisted surgery
* Synthetic biology
* Synthetic genomics
* Virotherapy
* Oncolytic virus
* Tricorder
* Whole genome sequencing

Displays|

| Next generation|

* FED
* FLCD
* iMoD
* Laser
* LPD
* OLED
* OLET
* QD-LED
* SED
* TPD
* TDEL
* TMOS
* MicroLED

|

Screenless|

* Bionic contact lens
* Head-mounted display
* Head-up display
* Optical head-mounted display
* Virtual retinal display

Other|

* Autostereoscopy
* Flexible display
* Holographic display
* Computer-generated holography
* Multi-primary color display
* Ultra HD
* Volumetric display

Electronics|

* Electronic nose
* E-textiles
* Flexible electronics
* Molecular electronics
* Nanoelectromechanical systems
* Memristor
* Spintronics
* Thermal copper pillar bump
* Twistronics

Energy|

| Production|

* Airborne wind turbine
* Artificial photosynthesis
* Biofuels
* Carbon-neutral fuel
* Concentrated solar power
* Fusion power
* Home fuel cell
* Hydrogen economy
* Methanol economy
* Molten salt reactor
* Nantenna
* Photovoltaic pavement
* Space-based solar power
* Vortex engine

|

Storage|

* Beltway battery
* Compressed air energy storage
* Flywheel energy storage
* Grid energy storage
* Lithium–air battery
* Molten-salt battery
* Nanowire battery
* Research in lithium-ion batteries
* Silicon–air battery
* Thermal energy storage
* Ultracapacitor

Other|

* Smart grid
* Wireless power

Information and
communications

* Ambient intelligence
* Internet of things
* Artificial intelligence
* Applications of artificial intelligence
* Progress in artificial intelligence
* Machine translation
* Mobile translation
* Machine vision
* Semantic Web
* Speech recognition
* Atomtronics
* Carbon nanotube field-effect transistor
* Cybermethodology
* Fourth-generation optical discs
* 3D optical data storage
* Holographic data storage
* GPGPU
* Memory
* CBRAM
* FRAM
* Millipede
* MRAM
* NRAM
* PRAM
* Racetrack memory
* RRAM
* SONOS
* Optical computing
* RFID
* Chipless RFID
* Software-defined radio
* Three-dimensional integrated circuit

Manufacturing|

* 3D printing
* Claytronics
* Molecular assembler
* Utility fog

Materials science|

* Aerogel
* Amorphous metal
* Artificial muscle
* Conductive polymer
* Femtotechnology
* Fullerene
* Graphene
* High-temperature superconductivity
* High-temperature superfluidity
* Linear acetylenic carbon
* Metamaterials
* Metamaterial cloaking
* Metal foam
* Multi-function structures
* Nanotechnology
* Carbon nanotubes
* Molecular nanotechnology
* Nanomaterials
* Picotechnology
* Programmable matter
* Quantum dots
* Silicene
* Superalloy
* Synthetic diamond

Military|

* Antimatter weapon
* Caseless ammunition
* Directed-energy weapon
* Laser
* Maser
* Particle-beam weapon
* Sonic weapon
* Coilgun
* Railgun
* Plasma weapon
* Pure fusion weapon
* Stealth technology
* Vortex ring gun

Neuroscience|

* Artificial brain
* Brain–computer interface
* Electroencephalography
* Mind uploading
* Brain-reading
* Neuroinformatics
* Neuroprosthetics
* Bionic eye
* Brain implant
* Exocortex
* Retinal implant

Quantum|

* Quantum algorithms
* Quantum amplifier
* Quantum bus
* Quantum channel
* Quantum circuit
* Quantum complexity theory
* Quantum computing
* Quantum cryptography
* Quantum dynamics
* Quantum electronics
* Quantum error correction
* Quantum imaging
* Quantum information
* Quantum key distribution
* Quantum logic
* Quantum logic gates
* Quantum machine
* Quantum machine learning
* Quantum metamaterial
* Quantum metrology
* Quantum network
* Quantum neural network
* Quantum optics
* Quantum programming
* Quantum sensing
* Quantum simulator
* Quantum teleportation

Robotics|

* Domotics
* Nanorobotics
* Powered exoskeleton
* Self-reconfiguring modular robot
* Swarm robotics
* Uncrewed vehicle

Space science|

| Launch|

* Fusion rocket
* Non-rocket spacelaunch
* Mass driver
* Orbital ring
* Skyhook
* Space elevator
* Space fountain
* Space tether
* Reusable launch system

|

Propulsion|

* Beam-powered propulsion
* Ion thruster
* Laser propulsion
* Plasma propulsion engine
* Helicon thruster
* VASIMR
* Nuclear pulse propulsion
* Solar sail

Other|

* Interstellar travel
* Propellant depot
* Laser communication in space

Transport|

| Aerial|

* Adaptive compliant wing
* Backpack helicopter
* Delivery drone
* Flying car
* High-altitude platform
* Jet pack
* Pulse detonation engine
* Scramjet
* Spaceplane
* Supersonic transport

|

Land|

* Airless tire
* Alternative fuel vehicle
* Hydrogen vehicle
* Driverless car
* Ground effect train
* Hyperloop
* Maglev train
* Personal rapid transit
* Transit Elevated Bus
* Vactrain
* Vehicular communication systems

Pipeline|

* Pneumatic transport
* Automated vacuum collection

Other|

* Anti-gravity
* Cloak of invisibility
* Digital scent technology
* Force field
* Plasma window
* Immersive virtual reality
* Magnetic refrigeration
* Phased-array optics

Topics|

* Collingridge dilemma
* Differential technological development
* Disruptive Innovation
* Ephemeralization
* Exploratory engineering
* Fictional technology
* Proactionary principle
* Technological change
* Technological unemployment
* Technological convergence
* Technological evolution
* Technological paradigm
* Technology forecasting
* Accelerating change
* Moore's law
* Technological singularity
* Technology scouting
* Technology readiness level
* Technology roadmap
* Transhumanism

* Category
* List

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Original source: https://en.wikipedia.org/wiki/Regenerative medicine. Read more

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