Welcome to the second article of our Spotlight Series on one of the most exciting frontiers of scientific research and innovation, regenerative medicine.
In our first article, we answered the question “What is regenerative medicine?” and delved into the multi-disciplinary roles it encompasses, and explored some of the key technologies in the sector, including CAR-T cell therapies and bone marrow transplantation.
In this article, we take a look at the historical origins of regenerative medicine and how its therapies have come to transform human lives.
Where did it come from?
A key pillar of regenerative medicine, tissue regeneration, can be traced back to Greek mythology and the story of Prometheus, the Titan god of fire. Prometheus is said to have defied the gods by stealing fire and gifting it to humans who used it to progress scientific enquiry and advance civilisation. As punishment Zeus, king of the Olympian gods, sentenced the immortal Prometheus to eternal torment. Prometheus was bound to a rock, and during the day an eagle would peck at his liver – while at night, Prometheus’ liver would regenerate. The cycle repeated once dawn broke.
Fast forward to the present day, and scientists grow closer and closer to decoding exactly how whole organs can be regenerated – for far more altruistic purposes. The study of developmental biology has progressed to the point that scientists are able to harness the pluripotent abilities of embryonic stem cells in the laboratory. The process, called stem cell differentiation, utilises the right concoction of growth factors and proteins, applied at the appropriate concentrations, at key points of time intercepting the stem cell developmental trajectory to coerce stem cells to develop into a cell type of choice. Scientists are hopefully not far off applying an extension of this process to develop stem cells into organs and tissue in a process termed tissue engineering.
The hope is to one day harness methods of regeneration already seen in nature and apply this in human medicine. Scientists are presently studying axolotls (Ambystoma mexicanum), a salamander found in Mexico, for their ability to regenerate amputated limbs. This ability derives from the muscle, bone and skin cells at the amputation site to reprogram the genes that are “switched off”, causing these differentiated cells to revert to pluripotent stem cells. It is these pluripotent stem cells that are then able to differentiate and form all the different cell types necessary to regenerate the limb.
A history of regenerative medicine therapies
The ability to regenerate and repair the human body may seem miraculous, but the third of Arthur C Clarke’s Three Laws springs to mind – “any sufficiently advanced technology is indistinguishable from magic”. One of the first examples of regenerative medicine – blood transfusion – is relatively commonplace nowadays, but was considered a medical breakthrough when first undertaken in the 17th century. This was the first definitive example of taking functional cells from a donor human being and introducing them into a patient to restore normal function.
The next major advancement was a kidney transplantation that took place in 1954 between identical twins so there was no immune rejection of the donor organ.
Perhaps more notable however were the contributions of Nobel Prize winner Alexis Carrel, a French Surgeon, and Charles Lindbergh, the celebrated aviator, an unlikely pairing that set the scene for organ transplantation. Carrel, whose seminal work on cell culture and understanding how to keep organs alive outside the body, collaborated with Lindbergh in the 1930s to develop a perfusion pump that would be the basis of the development of the artificial heart.
A famous example of perhaps the first ‘modern day’ application of cell therapy was carried out by Dr Howard Green, a researcher at the Massachusetts Institute of Technology. Dr Green had earlier discovered that small patches of laboratory-grown skin could be grafted onto burn victims, leading to regeneration of the human skin. Dr Green was an attending doctor at the Massachusetts General Hospital in 1984 when he was asked to help two young brothers, Jamie and Glen Selby, who had suffered third-degree burns over almost their entire bodies in an horrific accident. Patches of skin were taken from the brothers and cultured in the lab, before being grafted on the young boys. Dr Green’s actions proved decisive, and without his intervention it’s unlikely the boys would have survived the accident.
This illustration of the potential of cell therapies to salvage the most catastrophic of circumstances inspired a wave of next generation therapies.
In the next part of the series, we discuss some of these therapies, and recent developments and trends in regenerative medicine.