CELL THERAPY AND STEM CELLS

K. Endo¹, T. Hata², K. Jobara², J. Iwasaki², S. Uemoto^3
1Hepatopancreatobiliary Surgery And Liver Transplantation, Graduate school of medicine, Kyoto University, Kyoto/JAPAN, ²Division Of Hepato-pancreato-biliary Surgery And Transplantation, Department Of Surgery, Kyoto University, Kyoto/JAPAN, ³Hepatopancreatobillary Surgery And Liver Transplantation, Kyoto University Hospital, Kyoto/JAPAN

Body: Introduction: Liver transplantation (LTx) is the most effective therapy for end-stage liver diseases. Graft shortage is a world-wide problem, which urges us to make efforts to expand the donor organ pool using extended criteria donors. The use of non-heart beating donors (NHBD) is regarded as one of the potential solutions for donor shortage, whereas liver transplantation from NHBD requires to solve the serious condition after prolonged warm ischemia, leading to a high frequency of primary graft non-function. Various strategies are being investigated to abrogate further injury to NHBD graft during retrieval, preservation, and reperfusion. Here, we have a strategy to repair and support the transplanted liver with simultaneous hepatocyte transplantation. Methods:In order to evaluate the feasibility of our strategy, we have developed the rat model of the heart-beating orthotopic liver transplantation (HB-OLTx) followed by intrasplenic hepatocyte transplantation (HTx). We used male Wistar and Lewis (LEW) rats as the donor and recipient of LTx, and Wistar and LacZ-transgenic LEW rats for hepatocyte donors. We performed HB-OLTx with HTx (1.0 x 10⁶ cells) (n=8) and HB-OLTx (n=3) as a controlgroup. Recipient rats were sacrificed and graft livers were examined histologically. Results: Compared to HB-OLTx, peri-operative mortality showed no disadvantage in HB-OLTx with HTx. Histologically, the hepatic tissue of the graft appeared normal without obvious necrotic lesion in the HB-OLTx with HTx (figure A), which indicated the absence of massive cell thrombosis. In X-gal staining, X-gal positive hepatocytes were distributed and colonized in hepatic lobules of the graft in the HB-OLTx with HTx sacrificed on post operative day 3 (figure B), which indicated the engraftment and survival of the transplanted hepatocytes. Conclusion: Although this strategy needs further investigation, our results suggest the possibility that transplanted hepatocytes might support the patient after LTx, as well as repair the damaged portions of the liver graft injured through warm ischemia and reperfusion in the poorly-conditioned NHBD LTx.

Disclosure: All authors have declared no conflicts of interest.