Mesenchymal Stem Cells for the Treatment of Liver Disease: Present and Perspectives
Abstract
Mesenchymal stem cell transplantation is an emerging therapy for treating chronic liver diseases. The potential of this treatment has been evaluated in preclinical and clinical studies. Although the mechanisms of mesenchymal stem cell transplantation are still not completely understood, accumulating evidence has revealed that their immunomodulation, differentiation, and antifibrotic properties play a crucial role in liver regeneration. The safety and therapeutic effects of mesenchymal stem cells in patients with chronic liver disease have been observed in many clinical studies. However, only modest improvements have been seen, partly because of the limited feasibility of transplanted cells at present. Here, we discuss several strategies targeted at improving viable cell engraftment and the potential challenges in the use of extracellular vesicle-based therapies for liver disease in the future.
INTRODUCTION
Chronic liver injury, such as that arising from viral infection, alcohol abuse, or metabolic diseases, causes liver cirrhosis and failure.1,2 The ultimate treatment for end-stage cirrhosis is liver transplantation.3 However, transplants are not readily available in many countries, and in countries where transplants are available, organ shortages and high costs related with transplantation make this an impractical option for many patients.
Stem cell transplantation has been proposed as a potential strategy for patients with hepatic diseases to prevent progression and treat those with advanced fibrosis. Stem cell transplantation including hematopoietic, induced pluripotent, and mesenchymal stem cells (MSCs) can be manipulated for division into hepatocyte-like cells both in vitro and in vivo.4,5 Of these cell types, MSCs have been shown to have the advantages of being obtained relatively easily and possessing low immunogenicity.6 They have self-renewal ability and can differentiate into cells of various lineages, including osteoblasts, adipocytes, and chondrocytes.7 Additionally, MSCs are safe in terms of ethical concerns because they do not originate from somatic cells. Furthermore, MSC transplantation has been considered safe and widely assessed in clinical settings of various diseases with promising results.8
The purpose of this review is to present the therapeutic effects of MSCs in liver diseases to address questions regarding efficacy, safety, and possible risks involved, as well as to discuss recent clinical advances involving clinical MSC-based therapies, opening a new path toward further studies.
