Cotransplantation of human stromal cell progenitors into preimmune fetal sheep results in early appearance of human donor cells in circulation and boosts cell levels in bone marrow at later time points after transplantation

Both in utero and postnatal hematopoietic stem cell (HSC) transplantation w ould benefit from the development of approaches that produce increased leve ls of engraftment or a reduction in the period of time required for reconst itution. We used the in utero model of human-sheep HSC transplantation to i nvestigate ways of improving engraftment and differentiation of donor cells after transplantation. We hypothesized that providing a more suitable micr oenvironment in the form of human stromal cell progenitors simultaneously w ith the transplanted hu-man HSC would result in higher rates of engraftment or differentiation of the human cells in this xenogeneic model. The result s presented here demonstrate that the cotransplantation of both autologous and allogeneic human bone marrow-derived stromal cell progenitors resulted in an enhancement of long-term engraftment of human cells in the bone marro w of the chimeric animals and in earlier and higher levels of donor cells i n circulation both during gestation and after birth. By using marked stroma l cells, we have also demonstrated that injected stromal cells alone engraf t and remain functional within the sheep hematopoietic microenvironment. Ap plication of this method to clinical HSC transplantation could potentially lead to Increased levels of long-term engraftment, a reduction in the time for hematopoietic reconstitution, and a means of delivery of foreign genes to the hematopoietic system. (Blood. 2000;95: 3620-3627) (C) 2000 by The Am erican Society of Hematology.