Heterotransplantation of the Kidney: Two Clinical Experiences

Reemtsma, K; McCracken, Brian H.; Schlegel, J.U.; Pearl, Maurice A.

doi:10.1126/science.143.3607.700

Cited by 94 publications

(24 citation statements)

References 3 publications

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“…First, acute vascular rejection is observed in allografts and concordant xenografts in which hyperacute rejection normally does not occur (10)(11)(12)(13)(14). Second, the pathology of acute vascular rejection, which is characterized by endothelial swelling, focal ischemia, and diffuse microvascular thrombosis consisting mainly of fibrin (6,14), differs from the pathology of hyperacute rejection, which is characterized by interstitial hemorrhage and platelet microthrombi (15,16).…”

Section: Introductionmentioning

confidence: 99%

The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.

Lin

Weidner²,

Byrne³

et al. 1998

J. Clin. Invest.

259

161

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Long-term success in xenotransplantation is currently hampered by acute vascular rejection. The inciting cause of acute vascular rejection is not yet known; however, a variety of observations suggest that the humoral immune response of the recipient against the donor may be involved in the pathogenesis of this process. Using a pig-to-baboon heterotopic cardiac transplant model, we examined the role of antibodies in the development of acute vascular rejection. After transplantation into baboons, hearts from transgenic pigs expressing human decay-accelerating factor and CD59 underwent acute vascular rejection leading to graft failure within 5 d; the histology was characterized by endothelial injury and fibrin thrombi. Hearts from the transgenic pigs transplanted into baboons whose circulating antibodies were depleted using antiimmunoglobulin columns (Therasorb, Unterschleisshein, Germany) did not undergo acute vascular rejection in five of six cases. Biopsies from the xenotransplants in Ig-depleted baboons revealed little or no IgM or IgG, and no histologic evidence of acute vascular rejection in the five cases. Complement activity in the baboons was within the normal range during the period of xenograft survival. In one case, acute vascular rejection of a xenotransplant occurred in a baboon in which the level of antidonor antibody rose after Ig depletion was discontinued. This study provides evidence that antibodies play a significant role in the pathogenesis of acute vascular rejection, and suggests that acute vascular rejection might be prevented or treated by therapies aimed at the humoral immune response to porcine antigens. (

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Section: Introductionmentioning

confidence: 99%

The role of antibodies in acute vascular rejection of pig-to-baboon cardiac transplants.

Lin

Weidner²,

Byrne³

et al. 1998

J. Clin. Invest.

259

161

View full text Add to dashboard Cite

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“…The concept of cross-species tissue transplantation has intrigued medical science for decades by its prospect of alleviating the constantly growing need for donor tissue (Reemtsma 1964; Kemp, 1996). The xenotransplantation paradigm is, however, severely hampered by the fact that cross-species grafts are invariably rejected in immunocompetent hosts.…”

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confidence: 99%

Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination

2008

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In spite of its immune privileged state, xenotransplantation within the CNS is associated with rapid graft destruction in immunocompetent hosts. Efforts to enhance graft survival have mostly focused on host immune response, whereas relatively little attention has been paid to donor tissue characteristics. In the present paper, we explore long-term survival of xenogeneic full-thickness neuroretinal transplants in immunocompetent hosts and investigate the significance of tissue integrity in relation to graft survival.Adult rabbits receiving no immunosuppression were used as hosts and fetal Sprague-Dowley rat neuroretina as donors. Using vitreoretinal surgical techniques, rabbits received either a full thickness or a fragmented neuroretinal graft to the subretinal space of one eye. Eyes receiving full-thickness grafts were examined morphologically after 91 days and fragmented grafts after 7-14 days.Surviving full thickness grafts were found in 6 out of 8 eyes, 4 of which displayed the normal laminated appearance. Major Histocompatibility Complex (MHC) up-regulation in surviving grafts was minimal and they contained a well organized photoreceptor layer, Protein Kinase C (PKC) labeled rod bipolar cells, parvalbumin labeled AII amacrine cells and glial fibrillary acidic protein (GFAP) labeled Müller cells. Fragmented grafts (n=6) were all destroyed or showed severe signs of rejection. A mass of inflammatory cells derived from the choroid was evident in these specimens, and no labeling of retina-specific cells were seen.We conclude that full-thickness rat neuroretina can survive for several months after subretinal transplantation to the subretinal space of immunocompetent rabbits, while fragmented counterparts are rapidly rejected. Surviving full-thickness grafts can develop many of the normal retinal morphological characteristics, indicating a thriving relationship between the initially immature donor tissue and its foreign host. Our results strongly indicates that donor tissue integrity is a crucial factor for graft survival in CNS xenotransplantation.

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“…In experimental systems, long term survival of . In 1964, 9 month survival was achieved in a chimpanzee-to-human renal transplant patient, using an immunosuppressive regimen of azathioprine, actinomycin C, and steroids 12 . In contrast to this, baboon-to-human xenografts are rejected despite modern immunosuppressive regimens 13 .…”

Section: Concordant Xenograf Tingmentioning

confidence: 99%