Giving everything you've got: Donating organs
As with blood, organ transplantation and donation is a much more complicated process than the "simple" replacement of a liver or kidney. On top of the extremely complicated and precise microsurgical intervention, there is also the imminent threat of organ rejection, where our body pecieves the new organ as a threat.
Transplantation is the process of moving cells, tissues, or organs, from one site to another, either within the same person or between a donor and a recipient. If an organ system fails, or becomes damaged as a consequence of disease or injury, it can be replaced with a healthy organ or tissue from a donor. However, organ transplantation is a major surgical undertaking and is only offered when all other treatment options have failed.
An old story
Successful human transplants have a long history of surgical skills developed long before the post-operative survival concerns were discovered. Rejection and the side effects of preventing rejection (especially infection and nephropathy) were, are, and may always be the key problem.
The first modern transplant – the implantation of organ tissue in order to replace an organ function – was a thyroid transplant in 1883. It was performed by the Swiss surgeon and later Nobel prize winner Theodor Kocher. The surgeon noticed that the complete removal of the thyroid organ lead to a complex of particular symptoms associated with a lack of thyroid hormone. Kocher reversed these symptoms by implanting thyroid tissue to these people and thus performed the first organ transplant. In the following years other surgeons, helmed by Kocher, used thyroid transplantation to also treat thyroid deficiency that appeared spontaneously, without a previous organ removal.
Pioneering work in the surgical technique of transplantation was made in the early 1900s by the French surgeons Alexis Carrel and Charles Guthrie, with the transplantation of arteries or veins. Their skillful anastomosis operations and the new suturing techniques laid the groundwork for later transplant surgery and won Carrel the 1912 Nobel Prize in Physiology or Medicine. The discovery of transplant immunity by the German surgeon Georg Schöne, various strategies of matching donor and recipient, and the use of different agents for immune suppression did paved the way for the organ transplantation we know today.
European allocation of organ donors
Eurotransplant is the european organization for organ transplant management and distribution. It is responsible for the allocation of donor organs in Austria, Belgium, Croatia, Germany, Hungary, Luxembourg, the Netherlands and Slovenia. This international collaborative framework includes all transplant hospitals, tissue-typing laboratories, and hospitals where organ donations take place. Eurotransplant allocated 6398 organs from deceased donors in 2021.
Kidney transplants are the most common organ transplanted, followed by the liver, lungs, heart and pancreas. However, whole organs are not the only type of transplant. The cornea, for example, is the most transplanted single tissue. Hematopoietic stem cell transplantation (HSCT), often called blood and marrow transplantation (BMT), is another common tissue transplantation procedure. Used to treat a broad spectrum of diseases, though most commonly for blood or bone marrow cancers such as leukemia and lymphoma, they compare in number with whole-organ transplants.
Table 1: Number of deceased donors allocated in 2021, by country and by organ. Note that one donor could provide more than one organ for transplantation.
A foreign body
The immune system plays a critical role in transplantation. The complex mechanisms of immunity, which under normal circumstances work to identify foreign microbes and direct the immune system to destroy them, pose a significant barrier to successful transplantation. Rejection of a transplant occurs where the immune system identifies the transplant as foreign, triggering a response that will destroy the transplanted organ or tissue.
The intensity of the immune response against the graft (donated organ or tissue) depends on the type of graft being transplanted and the genetic variety between the donor and recipient. To reduce the possibility of rejection, the donor and recipient are carefully matched for immune compatibility prior to transplantation. However, the small pool of eligible donors can make it difficult to find a donor-recipient match and there will always be a degree of rejection against the graft.
One of the first matches the donor and the recipient need to accomplish is the blood type match, consisting of the ABO and Rh factors (for more information about blood transfusion and blood types, read this article!). Then, the other 39 human blood group systems are checked, according to their severity of possible immune response and rejection consequences. Not all of them need to match – in fact, they never will in two individuals who aren't monozygotic twins – just enough of them do for our body to allow the new organ to coexist and not see it as a threat. The test is commonly referred to as the Panel-reactive antibody test.
Types of transplantation
There are several types of transplantation involving tissues and organs.
Autograft is the transplantation of cells, tissues or organs between sites within the same individual. Sometimes this is done with surplus tissue, tissue that can regenerate, or tissues more desperately needed elsewhere (examples include skin grafts, vein extraction and similar). Sometimes an autograft is done to remove the tissue and then treat it or the person before returning it (examples include stem cell autograft and storing blood in advance of surgery).
Allograft is the transplantation of organs or tissues from a donor to a non-genetically identical individual of the same species. Allografts are the most common type of transplant.Due to the genetic difference between the organ and the recipient, the recipient's immune system will identify the organ as foreign and attempt to destroy it, causing transplant rejection. The risk of transplant rejection can be estimated by measuring the Panel reactive antibody level.
Xenograft is the transplantation of an organ or tissue between two different species. An example is pig heart valve transplant, which is quite common and successful. Another example is attempted piscine-primate (fish to non-human primate) transplant of pancreatic tissue. This research study was intended to pave the way for potential human use, if successful. However, xenotransplantion is often an extremely dangerous type of transplant due to the increased risk of non-functional compatibility, rejection, and disease carried in the tissue. An ongoing study is focused on transplanting human fetal hearts and kidneys into animals, for future transplantation back into human patients. Success in this field would address the shortage of donor organs.
To reduce the risk of transplant rejection, patients are treated with immunosuppressive drugs that will dampen their immune response. Immunosuppressive drugs are given in two phases; an initial induction phase involving a high dose, and a later maintenance phase which involves using the drug in the long term at a lower dose.
The combination of drugs, and dosage given vary depending on the type of transplant and the chosen treatment regime. If a patient experiences an episode of acute rejection the drug combination is subject to change and the dosage is also likely to increase. Side effects can also cause alternative drugs to be used.
All current immunosuppressive drugs come with limitations, with one of the major ones being immunodeficiency. As they are non-specific, they will reduce the overall immune system function leaving patients susceptible to opportunistic infection (infections happening while our body is busy fighting something else, or when our body's defenses are low). Additionally, many of these drugs are associated with adverse side effects, such as high blood pressure, impaired renal function, diabetes mellitus, and increased risk of cancer – to name just a few. Patients are required to take a large number of immunosuppressants each day for the rest of their lives, which can have a major impact on their health and lifestyle. A fine balance is needd between suppressing immune function sufficiently to avoid rejection, preventing drug toxicity, and maintaining enough immune function to fight off disease.
A bright future
There is much work being done in the field of transplantation medicine, with various results. One of the most difficult approaches, but the most promising one is the use of 3D bioprinters for organ manufacture. In this approach, stem cells from the person in need of a new organ are collected and grown around an organ scaffold, recreating the organ with the exact cell imprint as the person's, with no risk of organ rejection. However, this method is still in its beginning phases and needs a lot of research. Other studies are done on better immunosuppressants, surgical extractions and supporting drugs.
There are over 100 000 people in Europe alone waiting for an eligible transplant, with more added each hour. Their number will only grow in the next decades due to our lifestyle, if the number of donors stays the same. Each donor can save multiple lives, donating liver, kidneys, heart, lungs and pancreas, and can enhance over 75 more, by donating tissues such as cornea, skin, bone marrow, blood and much more! We don't need them once we die, but somebody close to us might! Why not donate?
4. The effect of HLA‐C matching on acute renal transplant rejection. Frohn C., Fricke L., Puchta J-C., Kirchner H. Nephrology Dialysis Transplantation, Volume 16, Issue 2, February 2001, Pages 355–360, https://doi.org/10.1093/ndt/16.2.355
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