Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2017; 23(38): 6973-6982
Published online Oct 14, 2017. doi: 10.3748/wjg.v23.i38.6973
Adipose-derived stromal cells resemble bone marrow stromal cells in hepatocyte differentiation potential in vitro and in vivo
Li-Juan Xu, Shu-Fang Wang, De-Qing Wang, Lian-Jun Ma, Zheng Chen, Qian-Qian Chen, Jun Wang, Li Yan
Li-Juan Xu, Zheng Chen, Qian-Qian Chen, Li Yan, Department of Gastroenterology, Institute of Geriatrics, Chinese PLA General Hospital, Beijing 100853, China
Shu-Fang Wang, De-Qing Wang, Department of Blood Transfusion, Chinese PLA General Hospital, Beijing 100853, China
Lian-Jun Ma, Department of Endoscopics, China-Japan Union Hospital of Jilin University, Changchun 130000, Jilin Province, China
Jun Wang, Department of Gastroenterology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China
Author contributions: Xu LJ, Wang SF performed the research, analyzed the data, and wrote and revised the paper; Wang DQ provided the experimental site; Ma LJ, Chen Z, Chen QQ performed the research; Wang J and Yan L designed the research and participated in the revision of the paper; Xu LJ, Wang SF contributed equally to this work; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 30900669 and No. 81473271; Technology Nova Plan of Beijing City, No. 2011117; China Postdoctoral Science Foundation, No. 2016T90994.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Chinese PLA General Hospital, Beijing, China.
Institutional animal care and use committee statement: All experiments on animals were performed in accordance with the “Guide for the Care and Use of Laboratory Animals” (National Institutes of Health, 8th ed. 2011). All procedures involving animals were reviewed and approved by the Animal Care and Research Committee of Chinese PLA General Hospital, Beijing, China.
Conflict-of-interest statement: All the authors declare no potential conflict of interest related to this paper.
Data sharing statement: No additional data are available.
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/
Correspondence to: Li Yan, MD, PhD, Department of Gastroenterology, Institute of Geriatrics, Chinese PLA General Hospital, No. 28 Wanshou Road, Haidian District, Beijing 100853, China. yanlifmu@126.com
Telephone: +86-10-66876346 Fax: +86-10-66876346
Received: April 16, 2017
Peer-review started: April 27, 2016
First decision: June 22, 2017
Revised: July 20, 2017
Accepted: September 5, 2017
Article in press: September 5, 2017
Published online: October 14, 2017
Processing time: 182 Days and 9.1 Hours
Abstract
AIM

To investigate whether mesenchymal stem cells (MSCs) from adipose-derived stromal cells (ADSCs) and bone marrow stromal cells (BMSCs) have similar hepatic differentiation potential.

METHODS

Mouse ADSCs and BMSCs were isolated and cultured. Their morphological and phenotypic characteristics, as well as their multiple differentiation capacity were compared. A new culture system was established to induce ADSCs and BMSCs into functional hepatocytes. Reverse transcription polymerase chain reaction, Western blot, and immunofluorescence analyses were performed to identify the induced hepatocyte-like cells. CM-Dil-labeled ADSCs and BMSCs were then transplanted into a mouse model of CCl4-induced acute liver failure. Fluorescence microscopy was used to track the transplanted MSCs. Liver function was tested by an automatic biochemistry analyzer, and liver tissue histology was observed by hematoxylin and eosin (HE) staining.

RESULTS

ADSCs and BMSCs shared a similar morphology and multiple differentiation capacity, as well as a similar phenotype (with expression of CD29 and CD90 and no expression of CD11b or CD45). Morphologically, ADSCs and BMSCs became round and epithelioid following hepatic induction. These two cell types differentiated into hepatocyte-like cells with similar expression of albumin, cytokeratin 18, cytokeratin 19, alpha fetoprotein, and cytochrome P450. Fluorescence microscopy revealed that both ADSCs and BMSCs were observed in the mouse liver at different time points. Compared to the control group, both the function of the injured livers and HE staining showed significant improvement in the ADSC- and BMSC-transplanted mice. There was no significant difference between the two MSC groups.

CONCLUSION

ADSCs share a similar hepatic differentiation capacity and therapeutic effect with BMSCs in an acute liver failure model. ADSCs may represent an ideal seed cell type for cell transplantation or a bio-artificial liver support system.

Keywords: Adipose-derived stromal cells; Bone marrow stromal cells; Cell differentiation; Hepatocyte differentiation

Core tip: We investigated whether mesenchymal stem cells from adipose-derived stromal cells (ADSCs) and bone marrow stromal cells (BMSCs), have similar hepatic differentiation potential. We found that adipose-derived stromal cells resemble bone marrow stromal cells in their hepatocyte differentiation potential in vitro and in vivo. Because ADSCs are obtained more easily and less invasive than BMSCs, ADSCs might be more suitable seed cells for cell transplant or liver tissue engineering. We also developed a new protocol of preparing mouse BMSCs and established a new hepatic induction system.