Since ancient times, humans have told stories about the body’s natural ability to regenerate. In the 8th century B.C., the Greek poet Hesiod wrote about the regenerative capabilities of the Titan Prometheus’s liver:
“Here Prometheus was chained to a rock (or pillar) and Zeus sent an eagle to eat the Titan’s liver. Even worse, the liver re-grew every night and the eagle returned each day to perpetually torment Prometheus.”1
With access to only the most basic medical technologies, Hesiod astutely observed the liver’s natural capacity for regeneration — the greatest regenerative capacity of any internal organ, in fact.
Thousands of years later, scientists and researchers are beginning to understand and harness the body’s regenerative phenomena through the field of regenerative medicine. The practice is based on the idea that healing and restoration are preferable to symptom management, and that this is achievable by supporting the human body’s tendency to heal itself.
In recent years, regenerative medicine has been an increasingly present topic in the public media, responsible for promising and alarming headlines alike. Here, we’ll take a look at the roots of this exciting new medical field.
The current state of regenerative medicine is the result of 19th and 20th century advances in a variety of disciplines including tissue engineering, transplantation, cell biology, nanotechnology, molecular biology, genetics, biochemistry, and more. Two predecessors to regenerative medicine — transplantation and replacement therapies — saw several important advances beginning in the 1950s and 60s. These included many of the first transplants of vital organs as well as the first instance of cell transplantation in 1968.
Cook Myosite’s roots at the University of Pittsburgh are deeply entwined with early transplantation history. Henry Bahnson, then head of Department of Surgery at Pitt, performed Pennsylvania’s first heart transplant in 1968. The University of Pittsburgh Medical center (UPMC) rose to international renown with the addition of Dr. Thomas E Starzl in 1981. Dr. Starzl performed the world’s first liver transplant in Denver in 1963 and Pittsburgh’s first in 1981.2 His invaluable contributions to the field led to the renaming of the Pittsburgh Transplantation Institute to the Thomas E. Starlz Institute in 1996. Today, the Thomas E. Starlz Institute continues his legacy, administering world class clinical transplantation and pioneering the field with innovative scientific research.
Transplantation showed that healthy organs and cells could replace damaged or dysfunctional tissues. This process involved a certain degree of regeneration, as the new tissue must be assimilated into the recipient’s body. The 70s and 80s, however, saw the dawn of two new fields that rely almost entirely on regenerative mechanisms: tissue engineering and cell therapy.
In short, tissue engineering is the use of cells, engineering methods, and biological or artificial materials to improve or replace biological tissues, and cell therapy is the injection of specific kinds of cells into damaged or diseased tissues with the goal of healing that tissue.
Tissue engineering was proven to be possible in 1981 when the first engineered organ — an artificial skin made of plastics, cow tissue, and shark cartilage — was successfully used to treat severe burn victims. The discovery was the result of a collaboration between Dr. John F. Burke, a Harvard Medical School professor and surgeon at Massachusetts General Hospital, and Dr. Ioannis V. Yannas,3 a professor of fibers and polymers at the Massachusetts Institute of Technology.
Dr. Burke and Dr. Yannas — a doctor and an engineer — set an important example of what interdisciplinary collaborations can produce and provided one of the early major discoveries in a field that would become known as bioengineering.
“An important biological fact is that every part of us talks to every other part — all of our self interacts with all other parts,” said Dr. Burke in a 1981 interview with the New York Times.4 “We have a material now that does, in fact, interact with the patient so that the correct types of cells do the correct things as they grow.”
That year, a team of researchers across the Atlantic at Cambridge University was working on regenerative capacities from a different angle: stem cells. Sir Martin J. Evans and Dr. Matthew Kaufman had come up with the idea to use blastocysts to isolate embryonic stem cells, and they were able to successfully do so in mice.5 This was the first time stem cells had been isolated and cultured in a laboratory, and became the first in vitro stem cell line. This was also achieved independently by American researcher Gail R. Martin in the same year.6
These two discoveries, collectively encompassing engineering, genetics, cell biology, and more, provided much of the basis for the explosion of research in regenerative medicine that continues today. The fields of tissue engineering, cell therapy, and gene therapy (more on that in the next post) owe much of their foundational ideas to research that was done in the early late 70’s and early 80’s.
Regenerative medicine continued to advance at a rapid pace throughout the 90’s and into the 2000’s. 1997 saw the cloning of Dolly the sheep and the first approved autologous stem cell medicine by the FDA, Carticel™.7 Developed by Genzyme, Carticel™ received the first ever Biologics License Application (BLA) approval by the FDA. The treatment is comprised of cartilage cells and provides a barrier at bone-bone joints throughout the body, providing the patient with greater range of motion and mobility. Scientists collaborating between the University of Wisconsin-Madison and Johns Hopkins University were the first team to isolate human embryonic stem and human embryonic germ cells in 1998.8 A major milestone in regenerative medicine occurred in 20079 with the discovery of stem cells derived from amniotic fluid and placenta.
The development of these technologies over the last several decades has brought us to the current moment, where the human body’s natural regenerative capacity is finally beginning to be harnessed in FDA-approved therapies. As of July 2021, there are many FDA-approved tissue products in the United States and 22 FDA-approved cell or gene therapies. While the development and approval process of these innovative therapies is long, we are seeing so many new and novel therapies enter the market, providing hope for so many with rare and orphan diseases. With hundreds more in the pipeline and government initiatives supporting the development of regenerative medicines, that number will grow significantly over the next few years.
References:
[1] https://www.worldhistory.org/Prometheus/
[2] https://upmc.com/services/transplant/about/starzl-institute
[3] https://meche.mit.edu/people/faculty/YANNAS@MIT.EDU
[4] https://www.nytimes.com/2011/11/06/us/dr-john-f-burke-dies-at-89-created-synthetic-skin.html
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842209/
[6] https://www.hindawi.com/journals/sci/2018/1429351/
[7] https://pubmed.ncbi.nlm.nih.gov/16306015/
[8] https://science.sciencemag.org/content/282/5391/1145.abstract
[9] https://www.nature.com/articles/nbt1274
Additional Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823153/
https://www.unmc.edu/regenerativemed/about/whatis/history.html
https://link.springer.com/chapter/10.1007%2F978-94-007-5690-8_1
https://www.sciencedirect.com/science/article/pii/S2213879X1500053X
