My wife and I are avid fans of TV medical dramas—the list has been endless over the years of the various series that captured our interests. One of the reasons we enjoy medical shows so much is that it gives insight into cutting edge medical technology, and that was our business in our previous professional world.
In these TV shows, one of the more common medical issues that crop up is that a patient urgently requires an organ transplant, and the hunt for an appropriate donor evolves into the central crisis to be resolved. The simple big problem to solve is to find the best match that will elicit the least rejection by the recipient.
Acute rejection of a transplanted organ occurs to some degree in all transplants, except between identical twins. This results from antigen genetic markers and there are up to 8,000 known antigens carried by white blood cells (leukocytes) that cause a recipient patient to reject a transplanted organ, just as a patient’s body would reject and fight against a bacterial or viral infection. Often, close family relatives are better possible organ donors, but sometimes a total stranger will have compatible genetic markers.
Before the discovery of anti-rejection drugs, organ transplants were impossible—dooming the patient to a predictable death within a predictable time period. With anti-rejection drugs, which tap down the body’s immune system response to foreign tissue, organ donations and transplants are common practice.
The drugs that prevent organ rejection, however, are problematic in that by definition they suppress the patient’s immune system. This effect increases the risks of infection, cancer, increases cholesterol levels to sometimes dangerous levels, and increases the chance of diabetes and kidney failure. They also doom a transplant recipient to a life of taking up to 40 pills a day to prevent infections while tamping down the body’s natural immune system to accept the new organ.
In 1953, Dr. Peter Medawar and his British colleagues won a Nobel Prize for their research into training the immune systems of young mice to NOT reject tissue from unrelated mice by injecting the mice with white blood cells (the body’s primary immune response system) from unrelated mice.
This suggested that the body of a patient needing an organ transplant might be trained to accept an organ from someone considered not a near perfect medical match, and therefore the organ recipient would not need to receive a lifelong regimen of anti-rejection drugs and experience the dangerous side effects that are common with these drugs.
That research of fooling the immune system seemed to work in baby mice whose immune systems were still learning what was foreign and what was not, but that did not translate well to the already developed immune systems of adult mice when injecting the recipient mice with white blood cells from donors.
Present day medical science, however, has discovered that the immune response in humans are more precise than merely white blood cells. There are more specialized white blood cells in the human body, called regulatory T-lymphocytes (T cells), that regulate the body’s immune system to attack foreign tissue (as in a bacterial or viral infection, or a transplanted organ) but to prevent attacks on the body’s own tissue.
When T cells from an organ donor are harvested along with those of the organ recipient patient and grown together, they produce a modified T cell that can be injected into the recipient patient. These new T cells teach the immune system of the patient receiving a new organ to accept it as part of the patient’s body, rather than rejecting it, and thus requiring less anti-rejection drug therapy.
There is additional interesting research happening now that even drills down to more specific white blood cells, called regulatory dendritic cells, that help the body distinguish its own tissue and organs from transplanted ones. The advantage of dendritic cells is that these can be isolated from donor and recipient patients and modified to grow in one week, as opposed to several weeks for modified T cells, and still allow transplants without rejection.
This process has proved to be successful in a human trial in Pittsburgh with a patient receiving a liver transplant from an acceptable, yet not perfect, match. The recipient’s body learned to accept the new organ over time and the patient has now tapered down to only one anti-rejection drug. The patient’s doctors hope to even wean him from that one drug regimen in time.
Although this success involves only one patient, the medical team working with this process plan to do the procedure on 12 more patients. If successful, the doctors plan to expand the study with additional transplant patients at multiple test sites.
My takeaway from this research is that it promises a new hope to expand the science of organ transplantation—to remove some of the current barriers to organ transplantation in patients who remain further down on current transplant lists.
The current backlog of candidates on various transplant lists include (approximately) 95,000 for kidney, 13,000 for liver, 3,800 for heart, and 1,400 for lungs. In 2017, there were about 114,000 patients on various transplant waiting lists. Of those, less than 35,000 transplants were performed.
How wonderful it would be to be able to offer a future to more of those patients still remaining on those transplant lists.
Thoughts? Comments? I’d love to hear them!