Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2019; 25(41): 6190-6204
Published online Nov 7, 2019. doi: 10.3748/wjg.v25.i41.6190
Therapeutic potential of menstrual blood stem cells in treating acute liver failure
Pan-Pan Cen, Lin-Xiao Fan, Jie Wang, Jia-Jia Chen, Lan-Juan Li
Pan-Pan Cen, Department of Infectious Diseases, Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
Lin-Xiao Fan, Jie Wang, Jia-Jia Chen, Lan-Juan Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Author contributions: Cen PP and Chen JJ conceived and designed the research; Cen PP, Fan LX, and Wang J performed the experiments, and collected the data; Cen PP and Fan LX analyzed the data; Cen PP wrote the paper; all authors reviewed the paper; Li LJ provided financial support and gave final approval of the manuscript.
Supported by the State Key Laboratory for Diagnosis and Treatment of Infectious Disease; The First Affiliated Hospital of Zhejiang University School of Medicine, No. 2015KF04.
Institutional review board statement: This study was approved by the Institutional Review Board of the First Affiliated Hospital of Zhejiang University School of Medicine.
Institutional animal care and use committee statement: This study was approved by the Animal Care Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine (reference number: ZJU2015-511-09).
Conflict-of-interest statement: No competing financial interests exist.
Data sharing statement: (1) The copyright on any open access article in a journal published by BPG is retained by the authors; (2) Authors grant BPG the license to publish the article and identify itself as the original publisher; and (3) Authors grant any third party the right to use the article freely as long as its integrity is maintained and its original authors, citation details, and publisher are identified.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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/
Corresponding author: Lan-Juan Li, MD, PhD, Professor, Senior Researcher, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; First Affiliated Hospital of Zhejiang University School of Medicine, 48 Qingchun Road, Shangcheng District, Hangzhou 310003, Zhejiang Province, China. ljli@zju.edu.cn
Telephone: +86-571-87236759
Received: August 12, 2019
Peer-review started: August 12, 2019
First decision: August 27, 2019
Revised: September 11, 2019
Accepted: October 17, 2019
Article in press: October 17, 2019
Published online: November 7, 2019
ARTICLE HIGHLIGHTS
Research background

Acute liver failure (ALF) is a rapidly progressing liver disorder with extremely poor survival prognosis due to lack of effective treatment methods. In recent years, stem cell-based therapy has emerged as a new hope for revolutionizing the treatment of ALF. Thus, seeking for an ideal cell line for transplantation is of great importance.

Research motivation

Menstrual blood stem cells (MenSCs) are a group of easily accessible mesenchymal stem cells with advantages of a high level of immune privilege, robust replicative capacity and multipotential differentiation. However, little is known about the therapeutic effect of MenSCs in treating ALF in large animal models. MenSC transplantation could be a promising strategy for treating ALF.

Research objectives

The aim of this study was to investigate the efficacy of MenSCs for treating ALF in pigs and to dynamically trace the biodistribution of transplanted cells.

Research methods

MenSCs were labelled in vitro with the fluorescent dye PKH26. Phenotypic analysis of MenSCs was performed using a flow cytometer. Cell viability was assessed by CCK-8. Cell multipotential differentiation was assessed by osteogentic and adipogenic differentiation. ALF porcine model was induced with D-galactosamine at a dose of 1.0 g/kg. The treatment group received transplantation of PKH26-labelled MenSCs via the portal vein under B-ultrasound guidance. The liver, lungs and spleen of sacrificed animals were imaged with the In vivo Imaging System (IVIS) using a CCD camera.

Research results

The labelling procedure did not affect the morphology, viability or multipotential differentiation of MenSCs. The survival time was significantly prolonged, and the levels of ALT, AST, TBIL and PT were obviously decreased in the treatment group compared with the control group. The liver pathological tissue in MenSC treatment group showed obviously increased numbers of remaining hepatocytes and a comparatively slight necrotic degree and area. The IVIS imaging revealed that PKH26-positive MenSCs were clearly retained in the liver initially and then diffused through the systemic circulation. The homing ability of MenSCs was confirmed by the markedly increased signal intensity in the liver at 36 h after transplantation. However, to achieve the optimal effectiveness of MenSC therapy, the therapeutic dose, cell preconditioning, the timing of cell grafting and the delivery route need to be further investigated.

Research conclusions

This study showed that the immediate transplantation of MenSCs via the portal vein effectively improved liver function and coagulation, alleviated the progression of liver injury, and prolonged survival time. The study also demonstrated the ability of MenSCs to home to pathological hepatic environments after transplantation.

Research perspectives

The therapeutic effect and homing ability of intraportally transplanted MenSCs in a porcine ALF model have been confirmed. MenSC transplantation may be a promising strategy for treating ALF.