Xenogeneic bone marrow transplantation: II. Porcine‐specific growth factors enhance porcine bone marrow engraftment in an in vitro primate microenvironment

Abstract

Abstract: Establishment of mixed bone marrow chimerism in pig‐to‐primate transplantation, as a means of inducing specific immune tolerance, will require that both immune and nonimmune barriers be overcome. As a preliminary step in evaluating nonimmune barriers in this system, we have developed an in vitro model of engraftment in which long‐term culture of porcine bone marrow‐derived hematopoietic cells is supported on preformed primate bone marrow stromal layers. In the absence of cytokine supplementation, primate stromal cells were unable to support long‐term porcine hematopoiesis in these cultures. Supplementation with porcine Steel Factor was required for long‐term maintenance of hematopoietic progenitor cell content and total hematopoietic activity. Addition of porcine IL‐3, in combination with porcine Steel Factor, increased long‐term progenitor cell content and hematopoietic activity on primate stroma to levels comparable to that obtained in cultures on porcine stroma. The combination of porcine GM‐CSF and Steel Factor increased progenitor cell content and hematopoietic activity early in the cultures, but had little effect in long‐term cultures. The Steel Factor and IL‐3 combination was species‐specific in its action in these cultures, as the corresponding human cytokines were unable to effectively support long‐term porcine hematopoiesis. Likewise, the combination of porcine cytokines had only minimal effects on long‐term bone marrow culture of primate CD34+ cells I on primate stroma.