Regenerative medicine 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).
History
The ancient Greeks postulated whether parts of the body could be regenerated in the 700s BC. 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. 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. This began with cellular therapy, which led to the stem cell research that is widely being conducted today.
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. 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.
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.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. 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 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.
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.
Global Research Infrastructure 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. Research Current research in regenerative medicine spans a continuous spectrum from fundamental cell biology to clinical translational engineering, focusing on deciphering and manipulating the signaling pathways that govern tissue morphogenesis, cellular differentiation, and scarless wound healing. Rather than merely managing chronic symptoms, active laboratory investigations aim to understand why adult mammalian tissues lose the regenerative capacities inherent in lower vertebrates and human embryonic states. Research strategies are broadly categorized into three interdependent vectors: cell-based therapies, which isolate and direct stem cell fates; biomaterial design, which engineers bioactive scaffolds to mimic the native extracellular matrix; and the delivery of localized biochemical cues, such as growth factors and gene-editing complexes, to orchestrate endogenous tissue repair. A major bottleneck in ongoing research is solving the scalability of functional vascularization, as complex engineered tissues cannot survive past the limits of oxygen diffusion without an integrated capillary network.
Targeted Tissues and Organs
Cardiovascular tissues Cardiovascular regenerative medicine focuses on repairing damaged myocardial tissue, heart valves, and peripheral blood vessels, primarily targeting ischemic heart disease and congenital heart defects. Because adult mammalian cardiomyocytes possess highly restricted proliferative capacity, therapeutic strategies utilize engineered cardiac patches, cell-seeded hydrogels, and decellularized extracellular matrix (ECM) components to stimulate localized myocardial repair after a myocardial infarction. Clinical and pre-clinical research focuses heavily on using induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and vascular endothelial cells embedded within porous, biomimetic polymeric scaffolds to ensure functional electrical coupling and host tissue integration. Additionally, tissue-engineered vascular grafts (TEVGs) are investigated as synthetic or bio-resorbable alternatives for coronary artery bypass surgery, where scaffold porosity is precisely tuned to allow host cell infiltration, smooth muscle cell remodeling, and functional neovascularization without inducing thrombosis.
Pulmonary tissues