Tissue-Specific Differences in the Establishment of Tolerance

Vriens, Patrick W.; Nisco, Steven J.; Hoyt, E. Grant; Lyu, Shu‐Chen; Pierre, Peterson; Reitz, Bruce A.; Clayberger, Carol

doi:10.1097/00007890-199406270-00019

Cited by 2 publications

(1 citation statement)

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“…Prolongation of skin graft survival is generally considered the most stringent test for immunosuppressive or tolerance-inducing regimens in the field of transplantation 19;27;28 . While full durable tolerance was not achieved in this study, it nonetheless presents the first demonstration of the efficacy of hematopoietic cell transplantation in providing an immune modulating effect for porcine grafts transplanted to primate recipients.…”

Section: Discussionmentioning

confidence: 99%

Prolonged Survival of Pig Skin on Baboons After Administration of Pig Cells Expressing Human CD47

Tena¹,

Sachs

Mallard

et al. 2017

Transplantation

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Background Successful xenotransplantation will likely depend, in part, on the induction of immunological tolerance, since the high levels of immunosuppression otherwise required would likely have unacceptable side effects. Rapid clearance of administered porcine hematopoietic stem cells by primate macrophages has hampered previous attempts to induce tolerance through mixed hematopoietic chimerism across a pig-to-primate barrier. Phagocytosis is normally inhibited by binding of cell surface protein CD47 to macrophage SIRPα receptors. However pig CD47 has previously been shown to be ineffective in transducing signals through primate SIRPα. Methods Mobilized peripheral blood hematopoietic cells from transgenic swine expressing high or low levels of human CD47 were infused into conditioned baboons at 3 time points over a 9-week period. Xenogeneic peripheral blood chimerism was assessed following each infusion. Split thickness skin grafts from the hematopoietic cell donor swine were placed on recipients 5 weeks following the last cell infusion and 7 weeks following the discontinuation of all immunosuppression to test immune response. Results The level and duration of transient chimerism were substantially greater in baboons receiving hematopoietic cells from a pig expressing high levels of human CD47. Skin graft survival on high CD47 recipients was prolonged as well, in one case showing no signs of rejection at least 53 days following placement. Conclusions Prolongation of transient porcine chimerism via transgenic expression of human CD47 in a primate model is associated with an immune modulating effect, leading to markedly prolonged survival of donor swine skin xenografts that may be applicable to clinical solid organ xenotransplantation.

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Section: Discussionmentioning

confidence: 99%