Background: Our laboratory has previously described that in xenogeneic models (pig-to-primate) host macrophages participate in the clearance of porcine bone marrow cells when transplanted into baboons, hindering the ability to achieve mixed chimerism. CD47 interacts with SIRPΑ receptors on macrophages to inhibit their activation, but this interaction is species-specific. In order to inhibit host macrophage phagocytosis we generated a hCD47 transgenic swine on an -Α 1,3-galactosyltransferase null background (GalTKO-hCD47) to utilize as hematopoietic cell donors. We report the initial results of pig-to-primate bone-marrow transplantation using the GalTKO-hCD47 transgenic swine.
Methods: The GalTKO-hCD47 transgenic swine underwent cytokine induced mobilization via porcine SCF and IL-3. Peripheral stem and progenitor cells were then collected by two leukapheresis steps. Progenitor and stem cells were isolated as a ckit+ fraction by using MACS columns. Lymphocytes were collected for transplantation along with progenitor/stem cells. 7E+07 ckit+/kg and 3E+09 lymphocytes/kg were administered to two juvenile baboons that had undergone a non-myeloablative preparative regimen prior to cell transplantation.
Results: Flow cytometric analysis in blood samples showed detectable porcine cells circulating in the periphery from 5 hours to 4 days post-transplant. Despite the fact that porcine Colony Forming Units (CFU) were not detected in bone marrow aspiration samples taken at 28 days, there was no increase in the IgM and IgG levels of circulating antibody at any time after cell transplantation. Both animals also showed specific porcine unresponsiveness in Mixed Lymphocyte Reaction (MLR) and Elispot assays on day 48 after transplantation. Chimerism was detected again for 4 days in peripheral blood in both animals after they received a second cell transplantation.
Conclusions: Utilizing GalTKO-hCD47 transgenic swine as donors, we have observed for the first time a marked increase in duration of porcine hematopoietic cell chimerism in the baboon circulation as well as the induction of specific unresponsiveness to porcine cells in vitro by MLR and Elispot assays. The effect of this treatment on the induction of tolerance in vivo is under investigation.
To cite this abstract in AMA style:Tena A, Leonard D, Tasaki M, Mallard C, Germana S, Terlouw S, Dobrinsky J, Mtango N, Verstegen J, Sachs D, Hawley R. GalKO-hCD47 Transgenic Hematopoietic Stem and Progenitor Cells for Induction of Mixed Xenogeneic Chimerism in Primates: Initial Results [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/galko-hcd47-transgenic-hematopoietic-stem-and-progenitor-cells-for-induction-of-mixed-xenogeneic-chimerism-in-primates-initial-results/. Accessed April 7, 2020.
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