Livng-donor liver transplantation combined with donor-derived bone maroow hematopoietic cells as a treatment for advanced hepatocellular carcinoma

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We established a bone marrow transplantation (BMT) model in mice. Preconditioning for BMT was performed with an anti-tumor agent, cyclophosphamide (CYP). BALB/c and C57BL/6 mice were used as recipients and donors. Donor-derived bone marrow cells were transplanted to the recipient after administration of CYP at a dose of 200mg/kg. Consequently, tumor-bearing mouse model was established with a BALB/c mouse-derived tumor cell line, colon 26 to evaluate graft-versus-tumor effect by BMT. Cells of colon 26 was injected subcutaneously to the recipient, and donor-derived bone marrow cells or splenocytes were transplanted alter CYP preconditioning. Allogeneic BMT exerted significant anti-tumor effect. However, many recipients died of systemic GVHD. Then we tried to develop new protocols to control GVHD in an allogeneic rat models in which serial blood monitoring of chimerism can be performed easily. A reduced dose of CYP (150mg/kg) was found to induce bone marrow chimerism without GVHD. Additionally transient use of FK506 inhibited GVHD even with a dose of 200mg/kg CYP. With this protocol donor-specific tolerance was established in a heart transplantation model and MLR. Because this protocol have anti-tumor effect and does not require chronic immunosuppression, it may be applied to liver transplantation for advanced hepatocellular carcinoma.