Transplantation of gene-modified human bone marrow stromal cells into mouse-human bone chimeras

Transplantation of BM stromal cells engineered to secrete therapeutic facto rs could represent a treatment for a large array of hematologic disorders. The aim of this study was to evaluate the susceptibility of human BM stroma l cell precursors to retroviral gene transfer, then the ability of those to be transplanted in vivo. We have transduced a recombinant retrovirus encod ing the mouse CD2 antigen into STRO-1(+) cells selected from adult and feta l BM, Gene-modified stromal cells were injected intravenously into NOD-SCID mice engrafted previously with pieces of human fetal hematopoietic bone. U sing nested PCR, transgenic human cells were detected both in the marrow of human bone grafts and in the BM, liver, and spleen of host mice 7 weeks af ter grafting. These data indicate that BM stromal progenitor cells are targ ets for retrovirus-mediated gene transfer and can home to hematopoietic tis sues on engraftment through the bloodstream of nonconditioned hosts.