Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2017; 23(46): 8152-8168
Published online Dec 14, 2017. doi: 10.3748/wjg.v23.i46.8152
In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis
Guo-Zun Zhang, Hui-Cong Sun, Li-Bo Zheng, Jin-Bo Guo, Xiao-Lan Zhang
Guo-Zun Zhang, Hui-Cong Sun, Li-Bo Zheng, Jin-Bo Guo, Xiao-Lan Zhang, Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Guo-Zun Zhang, First Department of Gastroenterology, Cangzhou Central Hospital, Cangzhou 061001, Hebei Province, China
Hui-Cong Sun, Department of Internal Medicine, Ningbo Women and Children’s Hospital, Ningbo 315012, Zhejiang Province, China
Author contributions: Zhang GZ and Sun HC substantially contributed to the conception and design of the study and the acquisition, analysis and interpretation of the data; all authors drafted the article, made critical revisions related to the intellectual content of the manuscript, and approved the final version of the article to be published; Zhang GZ and Sun HC contributed equally to this manuscript.
Institutional review board statement: The study was reviewed and approved by the Hebei Medical University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Experimental Animal Center of Hebei Medical University (No. 911102).
Conflict-of-interest statement: We declare that there are no conflicts of interest to disclose.
Data sharing statement: Technical appendix, statistical code, and data set available from the corresponding author at xiaolanzh@126.com. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xiao-Lan Zhang, MD, PhD, Professor, Department of Gastroenterology, The Second Hospital of Hebei Medical University, 215 West Heping Road, Shijiazhuang 050000, Hebei Province, China. xiaolanzh@hb2h.com
Telephone: +86-311-66007370
Received: March 27, 2017
Peer-review started: March 29, 2017
First decision: May 3, 2017
Revised: May 29, 2017
Accepted: August 9, 2017
Article in press: August 9, 2017
Published online: December 14, 2017
Processing time: 260 Days and 11.6 Hours
Abstract
AIM

To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis.

METHODS

A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR.

RESULTS

We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of hUC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1.

CONCLUSION

Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

Keywords: Liver fibrosis/cirrhosis; Mesenchymal stem cells; Collagen metabolism; Hepatocyte; Differentiation

Core tip: Transplanted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could differentiate into hepatocytes in vivo, thereby reducing the activation state of hepatic stellate cells, decreasing collagen deposition, and enhancing extracellular matrix remodeling in liver cirrhosis. hUC-MSCs play an important role in treating liver fibrosis and cirrhosis.