Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2019; 11(8): 548-564
Published online Aug 26, 2019. doi: 10.4252/wjsc.v11.i8.548
Human umbilical cord mesenchymal stem cells ameliorate liver fibrosis in vitro and in vivo: From biological characteristics to therapeutic mechanisms
Fei Yin, Wen-Ying Wang, Wen-Hua Jiang
Fei Yin, Wen-Ying Wang, Wen-Hua Jiang, Department of Histology and Embryology, Basic Medical College of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Yin F wrote the manuscript; Wang WY collected the literature; Jiang WH revised the manuscript for important intellectual content.
Supported by the Natural Science Foundation of Jilin Province of China, No. 20190201010JC.
Conflict-of-interest statement: The authors of this manuscript have no conflicts of interest.
Open-Access: This article is an open-access article that 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:
Corresponding author: Wen-Hua Jiang, MD, Adjunct Professor, Department of Histology and Embryology, Basic Medical College of Jilin University, No. 126 Xinmin Street, Changchun 130021, Jilin Province, China.
Telephone: +86-13604321909
Received: February 18, 2019
Peer-review started: February 20, 2019
First decision: June 5, 2019
Revised: June 26, 2019
Accepted: July 17, 2019
Article in press: July 17, 2019
Published online: August 26, 2019

Liver fibrosis is a wound-healing response to chronic injuries, characterized by the excessive accumulation of extracellular matrix or scar tissue within the liver; in addition, its formation is associated with multiple cytokines as well as several cell types and a variety of signaling pathways. When liver fibrosis is not well controlled, it can progress to liver cirrhosis, but it is reversible in principle. Thus far, no efficient therapy is available for treatment of liver fibrosis. Although liver transplantation is the preferred strategy, there are many challenges remaining in this approach, such as shortage of donor organs, immunological rejection, and surgical complications. Hence, there is a great need for an alternative therapeutic strategy. Currently, mesenchymal stem cell (MSC) therapy is considered a promising therapeutic strategy for the treatment of liver fibrosis; advantageously, the characteristics of MSCs are continuous self-renewal, proliferation, multipotent differentiation, and immunomodulatory activities. The human umbilical cord-derived (hUC)-MSCs possess not only the common attributes of MSCs but also more stable biological characteristics, relatively easy accessibility, abundant source, and no ethical issues (e.g., bone marrow being the adult source), making hUC-MSCs a good choice for treatment of liver fibrosis. In this review, we summarize the biological characteristics of hUC-MSCs and their paracrine effects, exerted by secretion of various cytokines, which ultimately promote liver repair through several signaling pathways. Additionally, we discuss the capacity of hUC-MSCs to differentiate into hepatocyte-like cells for compensating the function of existing hepatocytes, which may aid in amelioration of liver fibrosis. Finally, we discuss the current status of the research field and its future prospects.

Keywords: Human umbilical cord mesenchymal stem cells, Liver fibrosis, Hepatocyte-like cells, Mechanism, Cell therapy, Paracrine effect, Exosome, Transdifferentiation

Core tip: Liver fibrosis is a major global health problem, for which no efficient therapy is available. Cell therapy, particularly involving human umbilical cord mesenchymal stem cells (known as hUC-MSCs), represents a promising therapeutic strategy, based mainly on the cells’ paracrine effects, transdifferentiation capacity and immunomodulatory function. In this review, we discuss the characteristics of hUC-MSCs, focusing on the possible mechanisms of these cells to ameliorate liver fibrosis, based upon evidence from in vitro and in vivo studies as well as ongoing clinical trials. This review also includes a discussion of the current status of the field and its future prospects.