Homing of liver-derived hemopoietic stem cells to fetal bone marrow.

Tissue distribution of HSC in fetal sheep was studied by in utero transplantation during the period when a switch in the site of hemopoiesis occurs from liver/spleen to the bone marrow. At day 50 of gestation, transplanted cells exclusively homed to the liver/spleen. By day 60, some HSC also homed to the marrow and, between days 60-80, their proportion in the marrow increased. By day 100 almost all engrafted donor HSC homed to the marrow. Nonetheless, expression of these stem cells did not occur in the blood until birth (day 145) when marrow assumed the function of hemopoiesis from liver/spleen. During this latter part of gestation, although homing sites in the marrow are available to transplanted HSC, the marrow does not contribute to the function of hemopoiesis. The significance of these observations in the context of in utero gene therapy via stem cell transplantation is discussed.