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Updated: May 6, 2026
piggyBac Transposon System Modification of Primary Human T Cells
Published on: November 5, 2012
Transgenic expression of human CD47 on pig cells provides only partial protection against human macrophage-mediated
Soha Mcheik1, Hui Wang1, Xiaolan Ding1
1Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, New York, USA.
Tolerance induction would prevent xenograft rejection while avoiding high levels of immunosuppression. Mixed chimerism is an attractive approach to xenotolerance induction, as it tolerizes T, B, and natural killer cells. However, the species-specific interaction between CD47 and signal regulatory protein alpha is ineffective in the pig-to-human combination and may limit pig cell and organ engraftment. Prior studies showed that human CD47 (hCD47) expression on porcine cells can inhibit phagocytosis by primate macrophages. We have now tested the effect of hCD47 expression on the destruction of pig splenocytes in a human immune system (HIS) mouse model. Although the hCD47 transgene enhanced the survival of opsonized and nonopsonized porcine splenocytes in both HIS mice and nonreconstituted immunodeficient (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice, macrophage-mediated destruction of hCD47-transgenic pig cells still occurred in HIS mice. In longer-term studies, higher levels of pig chimerism were achieved in HIS mice receiving hCD47-transgenic compared to control pig bone marrow cells. Taken together, these results indicate that transgenic expression of hCD47 may reduce macrophage-mediated xenograft rejection in clinical xenotransplantation, but that additional strategies are needed to fully overcome human macrophage-mediated destruction of pig cells.
Tolerance induction would prevent xenograft rejection while avoiding high levels of immunosuppression. Mixed chimerism is an attractive approach to xenotolerance induction, as it tolerizes T, B, and natural killer cells. However, the species-specific interaction between CD47 and signal regulatory protein alpha is ineffective in the pig-to-human combination and may limit pig cell and organ engraftment. Prior studies showed that human CD47 (hCD47) expression on porcine cells can inhibit phagocytosis by primate macrophages. We have now tested the effect of hCD47 expression on the destruction of pig splenocytes in a human immune system (HIS) mouse model. Although the hCD47 transgene enhanced the survival of opsonized and nonopsonized porcine splenocytes in both HIS mice and nonreconstituted immunodeficient (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice, macrophage-mediated destruction of hCD47-transgenic pig cells still occurred in HIS mice. In longer-term studies, higher levels of pig chimerism were achieved in HIS mice receiving hCD47-transgenic compared to control pig bone marrow cells. Taken together, these results indicate that transgenic expression of hCD47 may reduce macrophage-mediated xenograft rejection in clinical xenotransplantation, but that additional strategies are needed to fully overcome human macrophage-mediated destruction of pig cells.
