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(Purpose) Recent studies demonstrated that transplantation of bone marrow cells (BMCs) raises hepatocytes in the host liver. And transplantation of liver nonparenchymal cells (LNPCs) into the lethally-irradiated rats was shown to reconstitute the bone marrow of the recipients. We previously showed that, when Fischer 344 rats (F344) BMCs were transplanted into the portal vein of F344 congenic Nagase’s analbuminenic rats (F344alb) immediately after 70% hepatectomy or into the penile vein after whole body irradiation, colonies of albumin positive (alb+) hepatocytes of the F344 origin were formed within the host liver. In the present study, we investigated whether the BMCs derived from the F344 LNPCs can increase alb+ hepatocytes within the liver of F344alb in which the bone marrow was reconstituted by the transplantation with F344 LNPCs after whole body irradiation. (Materials and Methods) The liver was flowed through via the portal vein with Hanks’ solution, followed by perfusion with a 0.05% collagenase solution. LNPCs were collected from the supernatants by centrifugation at 400 g for 5 min and suspended in the Hanks’ solution. The LNPCs (107 cells/animal, viability of >85%) were infused into the penile vein of the recipients immediately after whole body irradiation (7.5 Gy/rat), and the recipients were sacrificed 8 weeks later. (Results) Eleven of 15 F344alb that received the LNPC transplantation after irradiation survived, while only one of 8 F344alb that received irradiation alone was alive until 8 weeks. The normal albumin gene sequences were detected by PCR in BMCs of the recipient F344alb that received LNPC transplantation after irradiation, indicating that the F344alb bone marrow was reconstituted by F344 LNPCs. Clusters consisting of more than 3 alb+ hepatocytes were detected in the livers of F344alb with the LNPC or BMC transplantation after irradiation together with single or double alb+ cells. The normal albumin gene sequences were detected by PCR in the DNA isolated from such alb+ hepatocyte clusters microdissected from the immunostained sections. (Conclusion) The data indicate that the BMCs derived from the F344 LNPCs could increase alb+ hepatocytes within the F344alb liver.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA