Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 21, 2011; 17(19): 2397-2406
Published online May 21, 2011. doi: 10.3748/wjg.v17.i19.2397
Protective effects of ACLF sera on metabolic functions and proliferation of hepatocytes co-cultured with bone marrow MSCs in vitro
Xiao-Lei Shi, Jin-Yang Gu, Yue Zhang, Bing Han, Jiang-Qiang Xiao, Xian-Wen Yuan, Ning Zhang, Yi-Tao Ding
Xiao-Lei Shi, Jin-Yang Gu, Bing Han, Jiang-Qiang Xiao, Yi-Tao Ding, Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
Xiao-Lei Shi, Jin-Yang Gu, Yi-Tao Ding, Jiangsu Provincial Key Medical Center for Hepatobiliary Diseases, Nanjing 210008, Jiangsu Province, China
Xiao-Lei Shi, Jin-Yang Gu, Yi-Tao Ding, Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210008, Jiangsu Province, Jiangsu Province, China
Xiao-Lei Shi, Jin-Yang Gu, Yue Zhang, Bing Han, Jiang-Qiang Xiao, Xian-Wen Yuan, Yi-Tao Ding, Institute of Hepatobiliary Surgery, Nanjing University, Nanjing 210008, Jiangsu Province, China
Yue Zhang, Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing 210008, Jiangsu Province, China
Ning Zhang, Center for Artificial Liver Therapy, Nanjing Second Hospital, Nanjing 210008, Jiangsu Province, China
Author contributions: Shi XL and Ding YT designed the research; Gu JY, Zhang Y, Han B, Xiao JQ, Yuan XW and Zhang N performed the research; Shi XL analyzed the data and wrote the paper.
Supported by the National Natural Science Foundation of China, No.30772129 and Jiangsu Provincial Key Medical Center for Hepatobiliary Disease, No. ZX200605
Correspondence to: Yi-Tao Ding, Professor, Department of Hepatobiliary Surgery, Nanjing DrumTower Hospital, No. 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, China. yitaoding@hotmail.com
Telephone: +86-25-83304616 Fax: +86-25-83317016
Received: November 2, 2010
Revised: January 13, 2011
Accepted: January 20, 2011
Published online: May 21, 2011
Abstract

AIM: To investigate whether the function of hepatocytes co-cultured with bone marrow mesenchymal stem cells (MSCs) could be maintained in serum from acute-on-chronic liver failure (ACLF) patients.

METHODS: Hepatocyte supportive functions and cytotoxicity of sera from 18 patients with viral hepatitis B-induced ACLF and 18 healthy volunteers were evaluated for porcine hepatocytes co-cultured with MSCs and hepatocyte mono-layered culture, respectively. Chemokine profile was also examined for the normal serum and liver failure serum.

RESULTS: Hepatocyte growth factor (HGF) and Tumor necrosis factor; tumor necrosis factor (TNF)-α were remarkably elevated in response to ACLF while epidermal growth factor (EGF) and VEGF levels were significantly decreased. Liver failure serum samples induced a higher detachment rate, lower viability and decreased liver support functions in the homo-hepatocyte culture. Hepatocytes co-cultured with MSCs could tolerate the cytotoxicity of the serum from ACLF patients and had similar liver support functions compared with the hepatocytes cultured with healthy human serum in vitro. In addition, co-cultured hepatocytes maintained a proliferative capability despite of the insult from liver failure serum.

CONCLUSION: ACLF serum does not impair the cell morphology, viability, proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro.

Keywords: Acute-on-chronic liver failure serum; Primary hepatocytes; Bone marrow marrow mesenchymal stem cells; Co-culture; Hepatocyte-based modality