Xenogenic differentiation of human bone marrow stem cells into hepatocytes / 中国组织工程研究

ABSTRACT

BACKGROUND: How to obtain human-derived hepatocyte of high quality is the key problem for both bioartificial liver and hepatocyte transplantation. Bone marrow stem cells (BMSCs) can differentiate hepatocyte under proper condition, which provides a new think for obtaining hepatocyte.OBJECTIVE: To investigate the methods of the trans-differentiation of human BMSCs into hepatocyte in rats so as to provide a new think for clinical transplantation of liver and source of bioartificial liver.DESIGN: Randomized controlled study.SETTING: General Surgery of Zhujiang Hospital of Southern Medical University.MATERIALS The experiment was conducted at Central Laboratory of Zhujia ng Hospital of Southern Medical University from May 2004 to February 2005. Totally 40 male SD rats of clean grade were divided randomly into five groups model group, modeling + 14-day transplantation group of human BMSCs, modeling + 28-day transplantation group of human BMSCs, modeling + 14-day transplantation group of CL-1 cell (human hepatocyte family), and modeling + 28-day transplantation group of CL-1 cell (human hepatocyte family) with 8 in each group.acetaminofIuorene + carbon tetrachloride + cyclophosphamide were esand differentiated into hepatocyte with remedial liver regeneration. Human BMSCs were observed for 14 days in modeling + 14-day transplantation group of human BMSCs, for 28 days in modeling + 28-day transplantation group of human BMSCs, for 14 days in modeling + 14-day transplantation group of CL-1 cell and for 28 days in modeling + 28-day transplantation group of CL-1 cell. However, cells in model group function of rats was measured at normal state, before and after transplantation. The expressions of human albumin mRNA in liver were detected by immunohistochemistry staining, polymerase chain reaction (PCR) and real time reverse transcription polymerase chain reaction (RT-PCR) respectively.of human albumin mRNA in liver.transplantation of human BMSCs on hepatic function and content of total bilirubin Hepatic function and content of total bilirubin in each transplantation group were similar to those in model group at normal state and before transplantation (P ＞ 0.05); values in each group were obviously increased before transplantation as compared with those at normal state (P ＜ 0.01) and were obviously decreased after transplantation as compared with those before transplantation (P ＜ 0.01) but were higher ical section of hepatic cells At normal state, pathological section of hepatic cells showed that hepatic cells lined in strip-chorda shape and radian shape around central vein; and inflammatory cells were not infiltrated in crossed-channel area. Necrosis was observed in model group. Proliferated changes were observed in transplantation groups of human BMSCs after a few of necrosis, and ovale-round cells and small bile duct proliferation main histocompatibility antigen-I in liver Positive rate was 0 in model group; (13.03±0.18)% in modeling + 14-day transplantation group of human BMSCs; (9.47±0.46)% modeling + 28-day transplantation group of human BMSCs; (10.27±0.50)% in modeling + 14-day transplantation group of CL-1 cell; and (9.84±0.23)% in modeling + 28-day transplanwas detected in model group, but Sox11 and Alu-sx were detected in both transplantation groups of human BMSCs and CL-1 cells at various RT-PCR Expression of human albumin mRNA was not observed in model group, but expression of that was observed in transplantation groups of human BMSCs and CL-1 cell as well as positive controls at various time points respectively.CONCLUSION: Human BMSCs can promote recovery of hepatic function.Replaceable rate of human-derived cells is 10% in liver of rats, which suggests that human BMSCs can converse into hepatocyte in xenoma and replace partly.