Multilineage engraftment in NOD/LtSz-scid/scid mice from mobilized human CD34+ peripheral blood progenitor cells

Abstract

Peripheral blood progenitor cells (PBPCs) are now the most widely used source for hematopoietic support of patients in the autologous transplant setting and are increasingly being used for allogeneic transplantation. A reliable model to characterize the in vivo potential of various PBPC subpopulations could be valuable as a preclinical assay to predict the hematopoietic performance in humans of these populations and of products resulting from their manipulations ex vivo. We have used immunocompromised nonobese diabetic/LtSz-scid/scid (NOD/SCID) mice to engraft human CD34+ PBPCs and to study the repopulation characteristics of this progenitor cell fraction. Following myeloablation, intravenous infusion of CD34+ cells consistently produced engraftment and development in mice. Multilineage development occurred in all mice with CD34+ cells, erythroid precursors, and the most immature populations of myeloid cells and B lymphocytes restricted to the mouse bone marrow (BM). More mature populations of myeloid cells and B lymphocytes were peripheralized to the spleen and blood of the animals. This finding suggests that human hematopoiesis in the mice may recapitulate hematopoietic recovery in humans. The provision of human growth factors was not necessary for either engraftment or development of CD34+ cells. When mice were supplemented with growth factors, engraftment levels were unaffected but development was biased toward myeloid production. These findings indicate that providing nonphysiological levels of human growth factors may obscure or enhance the developmental potential of particular progenitor cell populations in this model. Cells capable of initiating colony formation in vitro were maintained in BM during the engraftment period (up to 17 weeks), suggesting that continuous production of myeloid and erythroid precursors occurred from more primitive hematopoietic cells subsequent to engraftment. In comparing results from this study with previous results, it was found that in this model the engraftment potential of CD34+ umbilical cord blood cells is greater than that described here for CD34+ PBPCs. In summary, this model may provide a reliable assay to predict the hematopoietic potential of progenitor cell populations in humans if a correlation for engraftment of identical cell fractions can be established between the two species.