First baboon to human liver transplant
PITTSBURGH, June 29, 1992--Surgeons from the University of Pittsburgh Medical Center (UPMC) announced on June 29, 1992, that they transplanted a liver from a baboon into a 35-year-old male. The 11-hour operation, which began at Pitt's Presbyterian University Hospital at 11:24 a.m. on June 28, marks the first known baboon-to-human liver transplant in the world.
The surgery was performed by Satoru Todo, M.D., Andreas Tzakis, M.D., and John Fung, M.D., Ph.D., who are members of the Pitt transplant team under the direction of pioneer transplant surgeon Thomas E. Starzl, M.D., Ph.D. Twenty-nine years ago, Dr. Starzl was among the first to use animal organs in humans.
The recipient of the cross-species transplant, also called a xenotransplant, is a patient with chronic, active hepatitis B, a liver disease that will lead to death as it progresses.
Hepatitis B is considered by many members of the transplant community to be an absolute contraindication for liver transplantation because of the great likelihood the disease will recur in the newly transplanted liver.
"Baboons cannot be infected with hepatitis B, so as sources for organs, they may offer a solution for these patients," said Dr. Starzl, director of Pitt's Transplantation Institute.
"The baboon offers a distinct advantage to the patient with hepatitis B -- a chance to live. For all transplant candidates, xenotransplantation with organs from baboons or other animals can offer a predictable, ready supply of organs. This would, in turn, result in fewer patients dying while waiting and allow us to operate on an elective basis, before patients are literally at death's door," claimed Dr. Starzl.
"An animal organ may also be used as a temporary measure to sustain life until a human donor is available," added Satoru Todo, M.D., an associate professor of surgery.
Xenotransplantation has long been considered an answer to the critical shortage of available human donor organs. While patient waiting lists have become longer, the inadequate supply of donor organs persists. Nationwide, at least one patient dies each day while waiting for a liver transplant, and this figure has increased each year.
According to Dr. Starzl, recent research advances, particularly those related to drugs which interact with the immune system, have enabled his team to perform the operation.
"For the despairing liver transplant candidates at Pitt and elsewhere, the timing of these developments is a Godsend," Dr. Starzl said.
"Combatting rejection, especially in a xenotransplant model, is the ultimate challenge faced by those engaged in transplantation research. We believe we now have an effective combination of drugs capable of suppressing the recipient's immune system so that the foreign, animal organ is not rejected," added Dr. Fung, chief of transplantation at Pitt, referring to the drugs FK506, cyclophosphamide, prostaglandin, and prednisone.
FK506, a drug manufactured by Fujisawa Pharmaceutical Co., Ltd., of Japan and developed at Pitt to combat rejection, works to suppress the recipient's T-cells from attacking the donor organ. T-cells are one type of white blood cell important to the immune system.
Cyclophosphamide, a Bristol-Myers Squibb drug developed to treat cancer, was shown to hold promise for transplant recipients by Dr. Starzl more than 20 years ago. Commercially known as Cytoxan, cyclophosphamide prevents B-cells, another type of white blood cell, from proliferating, a process which occurs in the presence of an antigen -- a foreign substance -- and results in the production of antibodies. Antibodies help destroy the foreign substance.
Prednisone is a steroid hormone that affects those cells which help recognize and process antigens, while prostaglandin serves to subdue the chain reaction of events likely to occur in the immune system.
Collectively, these contain the forces that can prevent both forms of rejection from occurring: cellular rejection, which involves T-cells; and humoral rejection, when B-cells activate the production of antibodies. Early rejection in xenotransplantation primarily involves the humoral response and can be rapid and uncontrollable if the recipient has natural antibodies to another species' antigens. Pitt researchers conducted laboratory studies which found no natural antibodies specific to baboon antigens in the human immune system.
"Another point in our favor is the liver itself. In humans, we have found the liver to be more resistant to humoral rejection than any other organs which are transplanted. So, the main obstacle in xenotransplantation is lessened for the liver," said Dr. Tzakis, formerly an associate professor of surgery at the UPMC.
Prior to performing the surgery, the Pitt transplant program received the approval from the university's Institutional Review Board and Animal Use Committee and advised the Food and Drug Administration of its intent.
The baboon was selected as a source because it is not an endangered species, and can be bred safely and easily in captivity.
Although early attempts at xenotransplantation date back as far as 1905, new understanding of the immune system and subsequent new drugs created the scientific climate for several attempts in the 1960s, at a time when both dialysis treatment and cadaver organs were not widely available. In 1963 and 1964, Keith Reemtsma, M.D., performed chimpanzee-to-human kidney transplants in 12 adults at Tulane University. One recipient lived with the kidney for nine months without evidence of rejection before dying of an infection. Soon after this series, other surgeons made unsuccessful attempts to transplant a chimpanzee heart and kidney, and Dr. Starzl performed kidney transplants in six adults using baboon donors. The patients lived for 19 to 98 days after their transplants. Between 1969 and 1974, Dr. Starzl provided chimpanzee livers to three children, one of whom lived 14 days before succumbing to sepsis, a widespread infection. Surgeons at Loma Linda University had available the anti-rejection drug cyclosporine when Baby Fae received a baboon heart in 1984. The infant died of rejection 20 days after surgery. Between 1963 and 1984, 28 clinical procedures involving solid organs from animal donors were performed in the United States and South Africa.
# # #
MEDIA CONTACT: Lisa Rossi
Tel: (412) 647-3555 Fax: (412) 624-3184
동물 장기 이식 - Xenotransplantation on the
Web. 1999 All rights reserved.