Novel strategy for hepatocyte transplantation using resected organ with hepatocellular carcinoma or cholangiocarcinoma after hepatectomy.

Abstract

Although large hepatectomy (i.e., resection of 2-3 segments) is an increasingly common treatment for hepatocellular carcinoma and cholangiocarcinoma, it can lead to liver failure. However, a resected liver may contain large quantities of both normal hepatocytes (NHs) and carcinoma cells. We investigated separating these cell types so that NHs could be used as transplantable cells. Cancer cells were developed by immortalizing rat hepatocytes, using an artificial chromosome vector. Cancer cells and primary hepatocytes (PHs) were mixed in a 1:1 ratio, then separated into two groups using fluorescence activated cell sorting (FACS). Normal hepatocytes after FACS (NHaF) and cancer cells after FACS (CAaF) were transplanted into two spots on opposite sides of the backs of nude mice; and also into the spleens of three groups (NHaF, CAaF and controls) of non-albumin rats (NARs), from which we measured blood albumin levels, using ELISA. The PH and cancer cells were successfully separated using FACS. After separation, cancer cells transplanted subcutaneously in nude mice formed tumors, whereas transplanted PH cells in NARs only produced higher albumin levels. Transplanted NHaF cells did not produce tumors. However, this cells function was not enough in power for transplant source by this method. Nevertheless, we believe this technique can be improved and used to treat patients successfully.