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The History of Regenerative Medicine

Oh jeez. I can’t believe it’s been over a month since I posted anything. I’ve been crazy busy with my PhD and cubs recently.

I’ve been interested in the history of science for a number of years and the history of regenerative medicine does not disappoint. Surprisingly, the story begins as far back as 382-322 BC with the famous ancient Greek philosopher and scientist, Aristotle. He observed that the tails of lizards and snakes and the eyes of swallow chicks could regenerate.  In 77 AD, Roman scientist and author of Naturalis Historia, Pliny the Elder also commented on lizards’ ability to regrow their tails. That was old hat by now though so let’s jump forward to the 18th century. Regeneration was becoming an interesting area of research now. French scientist René-Antoine Ferchault de Réaumur wrote a paper on crayfish limb and claw regeneration in 1712. Dutch scientist Abraham Trembley then showed that when a hydra (small tentacled freshwater organism) was cut in half, it would regenerate into two separate animals. During this century, work on the regeneration of other organisms including earthworms and frogs were also conducted.

Moving forward to the 20th century, the first successful kidney transplant was performed by Joseph E Murray and colleagues at the Peter Bent Brigham Hospital in Boston in 1954. This was done on identical twin brothers to avoid immune rejection, the reason earlier transplant attempts had failed. In 1958, English scientist John Gurdon at the University of Oxford successfully cloned a frog. The 1960s then brought a number breakthroughs including the first liver and lung transplants in 1963, the first pancreas transplant in 1966 and even more impressive, the first heart transplant in 1967. Another important landmark was the first successful non-identical twin bone marrow transplantation in 1968. This was carried out by E. Donnall Thomas who went on to share the 1990 Nobel Prize in Physiology or Medicine with Joseph Murray for their pioneering work on organ and cell transplantation. Organ transplantation became far more common place in the 1980s with the development of immunosuppressive drugs such as cyclosporine. This markedly decreased the risk of rejection allowing transplants between non-identical twins to become feasible.

Let’s digress to the history of stem cells for a moment. Haematopoietic stem cells, which are found in bone marrow and blood and generate blood cells, were first described in 1961 by Canadian scientists Ernest McCulloch, John Till and colleagues. This was a very important discovery as haematopoietic stem cell transplantations are now used to treat diseases including leukaemia and myeloma. In 2014, a survey reported over 40,000 transplants took place in 49 countries. The cells I work on, mesenchymal stem cells (MSCs), were first described by Russian scientist Alexander Friedenstein and colleagues in the 1960s and 1970s. In 1981, mouse embryonic stem cells were isolated and grown in a lab.

Moving forward to the 1990s now, 1996 brought a huge landmark in cloning research. Ian Wilmut, Keith Campbell and colleagues from the Roslin Institute at the University of Edinburgh successfully cloned the first mammal and Dolly the sheep was born. The next breakthrough came just two years later in 1998 when a technique was developed to isolate and grow human embryonic stem cells in the lab. On the tissue engineering front, the first transplant of an artificial bladder grown in a lab from a patient’s own cells was carried out in 1999.

Coming into the 21st century now, I absolutely must mention Japanese scientist Shinya Yamanka for his game changing work on induced pluripotent stem cells. He demonstrated that adult somatic cells (all of our cells other than sperm, eggs and undifferentiated stem cells) could be reprogrammed back to pluripotency meaning they could be turned back into stem cells and become (differentiate) other cell types. Along with John Gurdon who worked on cloning frogs, he was awarded the 2012 Nobel Prize “for the discovery that mature cells can be reprogrammed to become pluripotent“. Moving forward to 2014, the first patient in Japan was treated with induced pluripotent stem cells and it restored her eyesight. In 2015, Holoclar became the first stem cell therapy given marketing approval in Europe by the European Medicines Agency. This is a treatment for limbal stem cell deficiency, a rare cause of blindness. Doing a quick a search of the clinical trials database (clinicaltrials.gov) there are over 2,500 ongoing clinical trials using stem cell therapies so it could be that in the next 5-10 years, we’ll see many more regenerative therapies appearing on the market!

I recently made a short video on this topic for my centre’s YouTube Channel:

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