İnsanlar arasında başarılı allotransplantların görece uzun bir tarihi vardır ki;henüz operasyon sonrası hastanın hayatta kalabilmesi için gerekli olan teknikler ortaya henüz çıkmamış iken operasyon teknikleri mevcuttu. Transplant reddi ve reddi önlemenin yan etkileri, (genellikle enfeksiyon ve nefropati) eskiden ve halen en önemli anahtar problemi oluşturmaktadır.
Çok eski çağlardaki bir kaç örnekten sonra görülen erken nakiller deri nakli ile başlar.İlk ciddi olgu burnun yeniden düzenlenmesi olan rinoplastinin hintli bir cerrah olan Sushruta tarafından milattan önce ikinci yüzyılda otogreft tekniği ile yaptığı cilt transplantasyonudur. Bu girişimlerin sonucunun başaraılı yahut da başarısız olduğu ise kayıtlı değildir.Yüzyıllar sonra italyan cerrah Gaspare Tagliacozzi başarılı cilt otogreftleri gerçekleştirdi.Ancak allogreftlerde başarısız oldu ve bu şekilde organ reddi mekanizması konusunda tartışmaları başlatmış oldu.
İlk başarılı allogreft nakli 1837 de bir ceylan üzerinde yapıldı; insandaki ilk başarılı kornea nakli ise Eduard Zirm tarafından Avusturyada 1905 yılında yapılmıştır. 1900lerin başında Fransız cerrah Alexis Carrel ve Charles Guthrienin arter ve ven nakli çalışmalarını geliştirmesi ile nakillerin cerrahi teknikleri daha da gelişmiş oldu. Onların bu yetenekli anastomosis operasyonları , yeni sütur teknikleri transplantasyon cerrahisinin gelişmesine büyük katkıda bulundu ve Carrel’a 1912 yılında tıp ve fizyoloji dalında Nobel ödülü kazandırdı. 1902 yılından itibaren Carrel köpekler üzerinde nakil deneyleri yaptı. Böbrek, kalpve dalak nakillerinde cerrahi başarı sağlamış olsa da onyıllarca aşılmaz bir engel olarak kalan organ reddi konusunda ilk çaresiz kalanlardan biriydi.
Cilt nakli konusunda en büyük adımlar Birinci dünya savaşı sırasında Harold Gillies‘in Aldershot’da yapmış olduğu çalışmalarla atıldı. Among his advances was the tubed pedicle graft, maintaining a flesh connection from the donor site until the graft established its own blood flow. Gillies’ assistant, Archibald McIndoe, carried on the work into World War II as reconstructive surgery. In 1962 the first successful replantation surgery was performed - re-attaching a severed limb and restoring (limited) function and feeling.
The first attempted human deceased-donor transplant was performed by the Ukrainian surgeon Yu Yu Voronoy in the 1930s; rejection resulted in failure. Joseph Murray performed the first successful transplant, a kidney transplant between identical twins, in 1954, successful because no immunosuppression was necessary in genetically identical twins.
In the late 1940s Peter Medawar, working for the National Institute for Medical Research, improved the understanding of rejection. Identifying the immune reactions in 1951 Medawar suggested that immunosuppressive drugs could be used. Cortisone had been recently discovered and the more effective azathioprine was identified in 1959, but it was not until the discovery of cyclosporine in 1970 that transplant surgery found a sufficiently powerful immunosuppressive.
Dr. Murray’s success with the kidney led to attempts with other organs. There was a successful deceased-donor lung transplant into a lung cancer sufferer in June 1963 by James Hardy in Jackson, Mississippi. The patient survived for eighteen days before dying of kidney failure. Thomas Starzl of Denver attempted a liver transplant in the same year, but was not successful until 1967.
The heart was a major prize for transplant surgeons. But, as well as rejection issues the heart deteriorates within minutes of death so any operation would have to be performed at great speed. The development of the heart-lung machine was also needed. Lung pioneer James Hardy attempted a human heart transplant in 1964, but a premature failure of the recipient’s heart caught Hardy with no human donor, he used a chimpanzee heart which failed very quickly. The first success was achieved December 3rd 1967 by Christiaan Barnard in Cape Town, South Africa. Louis Washkansky, the recipient, survived for eighteen days amid what many saw as a distasteful publicity circus. The media interest prompted a spate of heart transplants. Over a hundred were performed in 1968-69, but almost all the patients died within sixty days. Barnard’s second patient, Philip Blaiberg, lived for 19 months.
As mentioned, it was the advent of cyclosporine that altered transplants from research surgery to life-saving treatment. In 1968 surgical pioneer Denton Cooley performed seventeen transplants including the first heart-lung transplant. Fourteen of his patients were dead within six months. By 1984 two-thirds of all heart transplant patients survived for five years or more. With organ transplants becoming commonplace, limited only by donors, surgeons moved onto more risky fields, multiple organ transplants on humans and whole-body transplant research on animals. On March 9th 1981 the first successful heart-lung transplant took place at Stanford University Hospital. The head surgeon, Bruce Reitz, credited the patient’s recovery to cyclosporine-A.
As successful transplants and modern immunosuppression such as Tacrolimus (Prograf) in 1994, Mycophenolic acid (Cellcept or Myfortic) and Prednisone unsually used in conjunction with Ciclosporin make transplants more common and have improved the survival rate as these drugs are more effective in many patients than the previous generation of immunosuppression drugs. A new form of Ciclosporin is in clinical trials it is an Inhaled Cyclosporine and is being developed by Chiron Corp., the need for more organs has become critical. Advances in living-related donor transplants have made that increasingly common. Additionally, there is substantive research into xenotransplantation or transgenic organs; although these forms of transplant are not yet being used in humans, clinical trials involving the use of specific cell types have been conducted with promising results, such as using porcine islets of Langerhans to treat type one diabetes. However, there are still many problems that would need to be solved before they would be feasible options in patients requiring transplants.
Recently, researchers have been looking into steroid-free immunosuppression. This type of immunosupporession is being pioneered on large scale at Northwestern University in Chicago and other smaller institutions, while steroid minimization is being employed at the University of Wisconsin at Madison and other smaller institutions. This would avoid the side-effects of steroids. While short-term outcomes are outstanding, long-term outcomes are still unknown.
In addition, calcineurin-Inhibitor-Free Immunosuppression is currently undergoing extensive trialing, the result of which would be to allow sufficient immunosuppression, without the nephrotoxicity associated with standard regimens that include calcineurin inhibitors. Positive results have yet to be demonstrated in any trial.
An FDA approved immune function test from Cylex has shown effectiveness in minimizing the risk of infection and rejection in post-transplant patients by enabling doctors to tailor immunosuppressant drug regimens. By keeping a patient’s immune function within a certain window, doctors can adjust drug levels to prevent organ rejection while avoiding infection. Such information could help physicians reduce the use of immunosuppressive drugs, lowering drug therapy expenses while reducing the morbidity associated with liver biopsies, improve the daily life of transplant patients, and could prolong the life of the transplanted organ.
Başarılı organ nakilleri’nin geçmişi
- 1905: Eduard Zirm tarafından ilk başarılı kornea nakli
- 1954: Joseph Murray tarafından ilk başarılı böbrek nakli (Boston)
- 1966: Richard Lillehei ve William Kelly tarafından ilk başarılı pankreas nakli (Minnesota)
- 1967: Thomas Starzl tarafından ilk başarılı karaciğer nakli (Pittsburgh)
- 1967: Christiaan Barnard tarafından ilk başarılı kalp nakli (Cape Town, Güney Afrika)
- 1970: Robert White tarafından ilk başarılı maymun kafası nakli (Cleveland, A.B.D.)
- 1981: Bruce Reitz tarafından ilk başarılı kalp/akciğer nakli (Stanford)
- 1983: Joel Cooper tarafından ilk başarılı akciğer lobu nakli (Toronto)
- 1986: Joel Cooper tarafından ilk başarılı çift akciğer nakli (Toronto)
- 1987: Joel Cooper tarafından ilk başarılı tüm akciğer nakli (St. Louis)
- 1995: Lloyd Ratner ve Louis Kavoussi tarafından ilk başarılı laparoskopik canlı donör nefrektomisi (Baltimore)
- 1998: David Sutherland tarafından ilk başarılı canlı donör kısmi pankreas nakli (Minnesota)
- 1998: İlk Başarılı el nakli (Fransa)
- 2005: İlk Başarılı kısmi yüz nakli (Fransa)
- 2006: İlk Başarılı penis nakli (Çin)
