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
Abstract
BACKGROUND

Acute liver failure (ALF) is a significant and complex hepatic insult that may rapidly progress to life-threatening conditions. Recently, menstrual blood stem cells (MenSCs) have been identified as a group of easily accessible mesenchymal stem cells with the advantages of non-invasive acquisition, low immunogenicity, a greater capacity of self-renewal and multi-lineage differentiation, making them promising candidates for stem cell-based therapy to revolutionize the treatment strategies for liver failure.

AIM

To investigate the therapeutic potential of MenSCs for treating ALF in pigs and to dynamically trace the biodistribution of transplanted cells.

METHODS

MenSCs were labeled in vitro with PKH26, a lipophilic fluorescent dye. The treatment group received immediate transplantation of PKH26-labelled MenSCs (2.5 × 106/kg) via the portal vein after D-galactosamine injection, and the control group underwent sham operation. The survival time, liver function, and hepatic pathological changes were compared between the two groups. Three major organs (liver, lungs and spleen) were extracted from animals and imaged directly with the In vivo Imaging System (IVIS) at the predetermined time points. The regions of interest were drawn to quantify the cell uptake in different organs.

RESULTS

The labelling procedure did not affect the morphology, viability or multipotential differentiation of MenSCs. Biochemical analysis showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) and prothrombin time (PT) measured at selected time points 24 h after transplantation were significantly decreased in the treatment group (P < 0.05). The survival time of ALF animals was prolonged in the treatment group compared with the control group (75.75 ± 5.11 h vs 53.75 ± 2.37 h, log rank, P < 0.001). The liver pathological tissue in the MenSC treatment group showed obviously increased numbers of remaining hepatocytes and a comparatively slight necrotic degree and area. In addition, the IVIS imaging revealed that PKH26-positive MenSCs were clearly retained in the liver initially and then diffused through the systemic circulation. Interestingly, the signal intensity in the liver increased obviously at 36 h, which corresponded to the biochemical result that liver function deteriorated most rapidly at 24 - 36 h.

CONCLUSION

Our study demonstrates the therapeutic efficacy and homing ability of transplanted MenSCs in a large animal model of ALF and suggests that MenSC transplantation could be a promising strategy for treating ALF.

Keywords: Menstrual blood stem cell, Acute liver failure, Cell transplantation, Homing, Labelling

Core tip: In this study, we investigated for the first time the therapeutic potential of intraportally transplanted menstrual blood stem cells (MenSCs) in treating pigs with acute liver failure, and showed that MenSC treatment improved liver function and coagulation, alleviated the progression of liver injury, and prolonged the survival time of pigs. Additionally, ex vivo imaging also demonstrated the ability of MenSCs to home to pathological hepatic environments after transplantation. MenSC transplantation has the potential to be used as an available source for treating acute liver failure in future clinical therapy.