SIBLING ALLOGENEIC CELL TRANSPLANTS

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This project continues to focus on using genetic markers to track cells transplanted between MHC-matched, sex-mismatched sibling baboons. As every donor cell will contain a unique genetic marker, it is possible to assess the contribution of specific donor cell types to reconstitution of lympho-hematopoiesis in transplant recipients. We have previously demonstrated that not only can CD34+Lin- marrow cells repopulate all lineages after transplantation, animals thus reconstituted can have normal immune function [Andrews RG, et al. 1997 Blood 90:1701-1708]. More recently we have turned our attention to the role of CD34- cells in transplantation. Our recent studies, presented at the American Society of Hematology meeting, have demonstrated that in this primate model these cells contribute little to early hematopoietic reconstitution after transplantation. Further, they appear to be less than ideal targets for retrovirus-mediated gene transfer. In our studies to date we have not been able to detect any gene transfer into such cells after transplantation. Future studies will be directed toward the study of other non-retroviral vectors for transduction of this cell population in the context of allogeneic stem cell transplantation and determination of the function/existence of CD34- stem cells in vivo. FUNDING NIH grants RR00166, AI35191, CA15704, AI37747 and HL54881 and Amgen Corp. Allen, M.D., Gaur, L.K., Nelson, K., de Fries, R., Delio, P., Anasetti, C., and Andrews, R.G. Microchimerism is induced in unreleated primates without immunosuppression by immature CD34+ donor stem cells. Abstr. Internat. Congr. Immunol., New Delhi, November 1998. Shields, L.E. and Andrews, R.G. In utero engraftment of allogeneic CD34+ marrow cells in nonhuman primates relationship to the absolute number of cells. Abstr. 3rd Internat. Symp. on In Utero Stem Cell Transplantation and Gene Therapy, September 1998. Andrews, R.G., Heyward, S., Gough, M., Morris, J., Peterson, L., Potter, J., Miller, A.D., and Kiem, H-P. Differential transduction and engraftment of CD34+Lin-, CD34+Lin+, and CD34-Lin- marrow cells in baboons. Proc. Am. Soc. Hematol., December 1998 (abstract).