Zhang GZ, Sun HC, Zheng LB, Guo JB, Zhang XL. In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis. World J Gastroenterol 2017; 23(46): 8152-8168 [PMID: 29290652 DOI: 10.3748/wjg.v23.i46.8152]
Corresponding Author of This Article
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
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
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.
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.
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.
