Successful allogeneic bone marrow transplantation by injection of bone marrow stromal cells and the cytological and molecular-biological analyses of their role

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We have previously found that bone marrow transplantation (BMT) can be used to treat autoimmune diseases and that successful BMT can be achieved by BMT plus bone grafts even if in chimerism-resistant combinations such as [normal→ MRL/1pr] and [DAB/2→C57BL/6] (J.Immunol.152 : 3991, 1994 ＆ Exp.Hematol.23 : 347, 1995). Bone marrow stromal cells (BMSCs) of the recipients are replaced partially by donor-type BMSCs, indicating that donor-derived BMSCs migrate from the engrafted bones to the recipient bones and offer a suitable environment for donor hemopoietic stem cells (HSCs). I have investigated the role of BMSCs as BMT-facilitating cells and obtained the following results.1.After BMT plus bone grafts, donor-derived BMSCs can migrate into recipient thymus and participate there in positive selection (Exp. Hematol. 28 : 950, 2000).2.When recipient mice were injected HSCs along with donor BMSCs obtained after 3-4 week-culture, by portal vein (PV) route, hemopoietic colony fomation was markedly increased in the recipient spleen and finally higher survival rate could be achieved (but not intravenous (IV) route). Hematopoietic colonies composed of both donor hemopoietic cells and BMSCs do exist in the liver of these mice. These findings suggest trapped BMSCs and HSCs do form hemopoietic colonies in the liver and then migrate into recipient bone marrow and spleen to form CFU-S (Stem Cells 19 : 144, 2001).3.BMT of bone marrow cells by PV route, followed by additional administration of bone marrow cells by IV route, leads a successful reconstitution even if in chimerism-resistant combinations (Stem Cells in press).4.MHC class Ia (H-2 K and D loci) determines the restriction between HSCs and BMSCs (Stem Cells 19 : 46, 2001).