Successful allogeneic bmt by injection of bmcs from portal vein

Our serial studies of BMT through the intravenous (IV) route have demonstrated that successful allogeneic BMT (allo-BMT) can be achieved if donor bones (to recruit bone marrow stromal cells: BMSCs) are cografted with bone marrow cells even in chimerism-resistant combinations, such as [DBA/2→B6] (Exp. Hematol. 23:347, 1995) and [Normal MRL/lpr mice (J. Immunol. 152:3119,1994). Donor-type BMSCs were found in the host bone marrow and thymus. We have also found that MHC restriction exists between hemopoietic stem cells (HSCs) and BMSCs (Blood 89:49,1997). Here, we report on the importance of cografting BMSCs in allo-BMT via the portal vein (PV) route. A significant increase in the number of day 14-CFU-S was observed in the recipient mice portal venously injected with both HSCs and donor BMSCs cultured for 3–4 wks. Histological examination revealed that hematopoietic colonies composed of both donor hemopoietic cells and BMSCs co-exist in the recipient liver. Both survival and hemopoietic reconstitution in [DBA/2→B6] mice were also enhanced when injected via the PV but not IV. We have previously reported that HSCs trapped in the liver after injecting BMCs via the PV can induce clonal anergy of CD8 + T cells. In the present study, we have found that donor BMSCs trapped in the recipient liver support the hemopoietic colony formation of donor HSCs. The BMSCs also seem to protect the HSCs from the attack of radioresistant host M∅, T cells and NK cells. As a result, CFU-S formation markedly increases, and a higher survival rate can ultimately be achieved. Thus, MHC-compatible BMSCs can contribute greatly to successful allo-BMT.