XENOGENEIC BONE-MARROW TRANSPLANTATION .2. PORCINE-SPECIFIC GROWTH-FACTORS ENHANCE PORCINE BONE-MARROW ENGRAFTMENT IN AN IN-VITRO PRIMATE MICROENVIRONMENT

Establishment of mixed bone marrow chimerism in pig-to-primate transpl antation, as a means of inducing specific immune tolerance, will requi re that both immune and nonimmune barriers be overcome, As a prelimina ry step in evaluating nonimmune barriers in this system, we have devel oped an in vitro model of engraftment in which long-term culture of po rcine bone marrow-derived hematopoietic cells is supported on preforme d primate bone marrow stromal layers. In the absence of cytokine suppl ementation, primate stromal cells were unable to support long-term por cine hematopoiesis in these cultures, Supplementation with porcine Ste el Factor was required for long-term maintenance of hematopoietic prog enitor cell content and total hematopoietic activity. Addition of porc ine IL-3, in combination with porcine Steel Factor, increased long-ter m 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 progenito r cell content and hematopoietic activity early in the cultures, but h ad Little effect in long-term cultures. The Steel Factor and IL-3 comb ination was species-specific in its action in these cultures, as the c orresponding human cytokines were unable to effectively support long-t erm porcine hematopoiesis. Likewise, the combination of porcine cytoki nes had only minimal effects on long-term bone marrow culture of prima te CD34+ cells on primate stroma.