Chinese Journal of Tissue Engineering Research ›› 2013, Vol. 17 ›› Issue (53): 9132-9138.doi: 10.3969/j.issn.2095-4344.2013.53.006

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Intrasplenic delivery of xenogeneic hepatic progenitor cells ameliorates acute liver injury in rats

Wan Zhen1, 2, Zhang Xiao-gang1, 2, Zheng Xing-long1, 2, Ma Feng1, 2, Ma Jia1, 2, Xiang Jun-xi1, 2, Wang Hao-hua1, 2, Lü Yi1, 2   

  1. 1Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an  710061, Shaanxi Province, China; 2Institute of Advanced Surgery Technology and Engineering, Xi’an Jiaotong University, Xi’an  710061, Shaanxi Province, China
  • Revised:2013-09-24 Online:2013-12-31 Published:2013-12-31
  • Contact: Lü Yi, Ph.D., Professor, Doctoral supervisor, Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China; Institute of Advanced Surgery Technology and Engineering, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China luyi169@126.com
  • About author:Wan Zhen☆, Studying for doctorate, Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China; Institute of Advanced Surgery Technology and Engineering, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
  • Supported by:

    The National Natural Science Foundation of China, No. 30600575*, 30830099*

Abstract:

BACKGROUND: Adult hepatic progenitor cells transplanted into the liver can engraft and differentiate into hepatocytes. However, little evidence was available concerning whether heterogeneic hepatic progenitor cells can promote the restoration of acute liver damage and whether the microenvironment of spleen can promote the graft survival and differentiation into hepatocytes.
OBJECTIVE: To evaluate the effect of hepatic progenitor cell transplantation on acute liver injury and monitor the engraftment and hepatocytic differentiation of transplanted hepatic progenitor cells in the splenic parenchyma.
METHODS: Adult mouse derived progenitor cell line liver epithelial progenitor cells were cultured in vitro for long term. The acute liver injury model was established by intraperitoneal injection of CCl4 in combination with 2/3 partial hepatectomy, for transplantation of liver epithelial progenitor cells. The liver pathological changes were observed by hematoxylin-eosin staining at 1, 5, 14 and 21 days after hepatectomy. Serum transaminase levels were monitored using automatic biochemistry analyzer. The Sry sequence in the spleens was tested by PCR.Immunohistochemistry staining against CK-19 and Alb was performed to analyze the engraftment and hepatocytic differentiation of transplanted hepatic progenitor cells in the splenic parenchyma.
RESULTS AND CONCLUSION: Liver epithelial progenitor cells maintained normal proliferation and bipotential differentiation capacity after long-term culture in vitro. Compared with model group, hepatocyte edema was alleviated significantly, and serum alanine aminotransferase and aspartic transaminase levels were decreased remarkably after cell transplantation group. The Sry sequence was tested in spleen DNAs at 1, 5, 14 and 21 days post-transplantation. CK-19 positive cells existed in the splenic parenchyma throughout the study period. Alb-positive cells emerged at 5 days post-transplantation and the number of Alb-positive cells was gradually increased over time. Results show that hepatic progenitor cells engraft and differentiate into hepatocytes in rat splenic parenchyma successfully, and the transplantation can promote the recovery process from CCl4/partial hepatectomy induced acute liver injury.



中国组织工程研究
杂志出版内容重点:肾移植肝移植移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植组织工程


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Key words: cell transplantation, spleen, adult stem cells, cell differentiation, cells, cultured, carbon tetrachloride

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