Baboon-to-human liver transplantation

Starzl, Thomas E.; Fung, John J.; Tzakis, Andreas G.; Todo, Satoru; Demetris, Anthony J.; Marino, Ignazio R.; Doyle, Howard R.; Zeevi, Adriana; Warty, Vijay; Kusne, Shimon; Rudert, William A.; Trucco, Massimo; Michaels, Marian G.

doi:10.1016/0140-6736(93)92553-6

Cited by 417 publications

(173 citation statements)

References 22 publications

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…34). Death was caused by infectious complications and by complications of biliary stasis rather than rejection or GVHD (156). This means that successful clinical xenotransplantation must be visualized along the same lines of donor-recipient cellular migration and repopulation, as with allograft acceptance.…”

Section: Whole-organ Xenotransplantationmentioning

confidence: 99%

Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance

1993

View full text Add to dashboard Cite

Section: Whole-organ Xenotransplantationmentioning

confidence: 99%

Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance

1993

View full text Add to dashboard Cite

“…Circulating immune complexes appeared early, receded, and reappeared sporadically until the time of death. 8,9 Good control of adaptive immunity had unmasked a low-grade innate immune response which, we concluded, could not be treated safely, if at all, with any combination of agents currently available. Consequently, we canceled the last two patients in our series of four approved by the Institutional Review Board.…”

mentioning

confidence: 88%

“…Although it was anticipated that the xenografts would provide definitive, as opposed to bridge, function, both grafts failed after 70 and 26 days despite heavy immunosuppression with tacrolimus, cyclophosphamide, prostaglandin E 1 , and prednisone. 8,9 The liver xenografts showed no trace of the occlusive endotheliolitis that had been responsible for patchy gangrene of the 1963 kidney xenografts and in the baboon-heart xenograft of Leonard Bailey's Baby Fae case. 10 Cellular rejection was found in only 1 of the 14 biopsies or autopsy specimens from the two xenografts (n = 7 each).…”

mentioning

confidence: 97%

“…Upon close examination, a very fine microsteatosis was seen in the hepatocytes of both xenografts, which dramatically worsened over the next few days, especially in the second case. 8,9 The grafts had survived an aborted hyperacute rejection. Although IgM found in the 1-hour biopsy specimen had largely cleared at 12 days, significant amounts of IgG remained in the xenografts throughout the survival periods of both patients.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Will Xenotransplantation Ever Be Feasible?

Starzl¹

1998

Journal of the American College of Surgeons

View full text Add to dashboard Cite

In several recent conferences, the principal questions have been whether Xenotransplantation technology should be encouraged and, if so, how it should be regulated. Because the prospect of successful transplantation of animal organs into humans is still remote, the rush to achieve consensus about clinical application 1,2 would be inexplicable were it not for two ostensibly unrelated issues. The first is the small but undeniable theoretical hazard of causing new human infections with the intermingling of tissues from different species. The second, advanced by animal-rights advocates, concerns the spiritual and ethical relationship of humans to animals. CLOSELY RELATED SPECIESThe rhetoric of these discussions has been heightened by the fact that all clinical organ xenotransplantations attempted since 1963 have failed, including >25 involving subhuman primate donors (19 reported or unreported chimpanzees, 10 baboons, and 1 [or 2] Rhesus monkeys). This experience began with Reemtsma and associates, 3 who proved in 1963 that kidneys from at least two subhuman primate donor species (Rhesus and chimpanzee) would not be rejected hyperacutely by humans. In fact, one of his chimpanzee xenografts functioned for 9 months. However, Reemtsma was the first to recognize that the humanoid qualities and threatened extinction of the chimpanzee would prevent its widespread use as a donor.Later in 1963, a team at the University of Colorado/Minnesota showed that baboon kidneys also would escape hyperacute rejection. In contrast to the chimpanzee, baboons flourished, and still do, in southern and central Africa. The six baboon renal xenografts of 1963 supported dialysis-free life for 6-60 days before undergoing fierce cellular rejection. 4 In addition, all of the baboon kidneys had occlusive endotheliolitis that was severe enough to cause regional parenchymal infarcts and islands of gangrene. We concluded by early 1964 that this humoral component of xenograft rejection could not be controlled with cell-directed immune suppression (azathioprine and prednisone at the time). A moratorium was selfimposed on further attempts. This hiatus lasted for 28 years, until investigations by Murase and colleagues 5 with the hamsterto-rat model appeared to justify a further trial. In this strain combination, in which the immune barrier resembles that between the baboon and human, 6 the combination of T-cell-specific immune suppression with tacrolimus plus B-cell-directed cyclophosphamide permitted the unprecedented routine survival of heart and liver xenografts for >100 days.In June 1992 and January 1993, two baboon-to-human orthotopic liver transplantations were performed in patients with chronic end-stage organ failure caused by hepatitis B virus infection.

show abstract

“…10 A more immediate impact on organ shortage already has come from the widespread use of livers from "marginal donors," as first documented by Makowka et al 11 and Pruim et al 12 The definition of a marginal donor has varied in different reports, and recently has included obesity. 13,14 Two potential risk factors-age and gender-are relevant with all donors, no matter what the other circumstances of death.…”

mentioning

confidence: 99%

Effect of donor age and sex on the outcome of liver transplantation*1

et al. 1995

View full text Add to dashboard Cite

We correlated donor and recipient factors with graft outcome in 436 adult patients who underwent 462 liver transplants. Donor variables analyzed were age, gender, ABO blood group, cause of death, length of stay in the intensive care unit, use of pressors or pitressin, need for cardiopulmonary resuscitation, terminal serum transaminases, and ischemia time. Recipient variables analyzed were age, gender, primary diagnosis, history of previous liver transplant, ABO blood group, cytotoxic antibody crossmatch, United Network for Organ Sharing (UNOS) status, and waiting time (except for the cross-match results, they were all known at the time of the operation). The endpoint of the analysis was graft failure, defined as patient death or retransplantation. Using multivariate analysis, graft failure was significantly associated with donor age, donor gender, previous liver transplantation, and UNOS 4 status of the recipient. The effect of donor age became evident only when they were older than 45 years. Livers from female donors yielded significantly poorer results, with 2-year graft survival of female to male 55% (95% CI, 45% to 67%); female to female, 64% (95% CI, 54% to 77%); male to male, 72% (95% CI, 66% to 78%); and male to female, 78% (95% CI, 70% to 88%). The only donors identified as questionable for liver procurement were old (≥60 years) women in whom the adverse age and gender factors were at least additive. However, rather than discard even these livers, in the face of an organ shortage crisis, their individualized use is suggested with case reporting in a special category.As of January 4, 1995, 37,751 transplant candidates were registered on the national waiting list operated by the United Network for Organ Sharing (UNOS), the agency that coordinates organ allocation in the United States. This was a 391% increase from the 9,632 waiting in December 1986. Of the 37,751 in 1995, 4,039 were liver candidates, up from 449 in 1987 (a 900% increase). The supply of all organ donors had undergone a marginal increase between 1988 and 1990 (from 4,085 to 4,514), but has remained relatively stable since then: 4,531 in 1991, 4,521 in 1992, 4,849 in 1993, and 4,891 in 1994. The limited supply of organ donors has increasingly influenced the selection of candidates for liver transplantation, and is used at some institutions to justify restricting the availability of the procedure. 1 Although the exact magnitude of the organ deficit is not yet known, 2,3 the obvious gap between supply and need has stimulated the development of bioartificial liver assist devices, 4 utilization of living related liver donors, 5,6 use of non-heart beating donors, 7-9 and 18,19 or beyond 20 was followed by a flurry of confirmatory reports, 13,14,21,22 countered by descriptions of degraded results using geriatric livers. [23][24][25][26] Less has been written about the effect of donor sex on outcome after liver transplantation, although there is an extensive literature, recently summarized by Neugarten and Silbiger, 27 showing poorer re...

show abstract

Baboon-to-human liver transplantation

Cited by 417 publications

References 22 publications

Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance

Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance

Will Xenotransplantation Ever Be Feasible?

Effect of donor age and sex on the outcome of liver transplantation*1

Contact Info

Product

Resources

About