Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2018; 24(2): 237-247
Published online Jan 14, 2018. doi: 10.3748/wjg.v24.i2.237
Transplantation of bone marrow-derived endothelial progenitor cells and hepatocyte stem cells from liver fibrosis rats ameliorates liver fibrosis
Ling Lan, Ran Liu, Ling-Yun Qin, Peng Cheng, Bo-Wei Liu, Bing-Yong Zhang, Song-Ze Ding, Xiu-Ling Li
Ling Lan, Bo-Wei Liu, Bing-Yong Zhang, Song-Ze Ding, Xiu-Ling Li, Department of Gastroenterology and Hepatology, the People’s Hospital of Zhengzhou University (the Henan Provincial People’s Hospital), Zhengzhou 450003, Henan Province, China
Ran Liu, Department of Oncology, Henan Provincial Rongjun Hospital, Xinxiang 453000, Henan Province, China
Ling-Yun Qin, Department of Gastroenterology and Hepatology, the Children’s Hospital of Zhengzhou, Zhengzhou 450003, Henan Province, China
Peng Cheng, Intensive Care Unit, the Second Affiliated Hospital of Luohe Medical College, Luohe 462000, Henan Province, China
Author contributions: Lan L and Liu R contributed equally to this study and are the co-first authors; Lan L and Liu R designed the study; Lan L, Liu R, Qin LY, Cheng P and Zhang BY performed the study; Lan L, Liu R and Qin LY wrote the paper; Liu BW and Zhang BY established the rat models; Ding SZ and Li XL collected and analyzed the data.
Supported by the National Natural Science Foundation of China, No. 30900598; the Basic and Advanced Technology Research Program of Henan Province, No. 142300410380; and the Medical Science and Technology Project of Henan Province, No. 201303211.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Henan Provincial People’s Hospital, China.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use committee of the Animal Experiment Center of Henan Province, China [SCXK(Yu)2005-0001].
Conflict-of-interest statement: Potential conflicts of interest do not exist.
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: Ling Lan, PhD, MD, Associate Professor, Department of Gastroenterology and Hepatology, the People’s Hospital of Zhengzhou University (the Henan Provincial People’s Hospital), 7 Weiwu Road, Zhengzhou 450003, Henan Province, China. lanling95@163.com
Telephone: +86-371-65580603 Fax: +86-371-6596 4376
Received: September 30, 2017
Peer-review started: October 1, 2017
First decision: October 25, 2017
Revised: November 6, 2017
Accepted: November 22, 2017
Article in press: November 22, 2017
Published online: January 14, 2018
Processing time: 105 Days and 21.8 Hours
ARTICLE HIGHLIGHTS
Research background

Hepatic neovascularization and endothelial/sinusoidal remodeling are critical for the treatment of liver fibrosis, in addition to liver regeneration. Transplantation of bone marrow-derived endothelial progenitor cells (BM-EPCs) has potential roles in hepatic neovascularization, endothelial/sinusoidal remodeling and increased hepatic blood flow for the treatment of liver fibrosis. However, BM-EPCs were all derived from healthy rats in these studies. We sought to evaluate the feasibility of clinical application of autogenous EPCs therapy by using normal BM-EPCs obtained from liver fibrosis rats, and evaluated the effectiveness of combined transplantation of BM-EPCs and BDHSCs in vivo for the treatment of liver fibrosis.

Research motivation

The author observed the feasibility of obtaining normal BM-EPCs from the liver fibrosis environment in rats. We evaluated the effectiveness for treating liver fibrosis by combined transplantation of BM-EPCs and bone marrow-derived hepatocyte stem cells (BDHSCs) in order to achieve the dual effects of hepatic neovascularization and liver regeneration. These findings highlight the clinical value of EPCs autotransplantation, and potential application of a novel strategy of therapy for liver fibrosis that involves combined transplantation of BM-EPCs and BDHSCs.

Research objectives

Our research objectives were to explore the feasibility of obtaining normal BM-EPCs from the liver fibrosis environment and the effectiveness for treating liver fibrosis by combined transplantation of BM-EPCs and BDHSCs. The significance of realizing these objectives were to highlight the clinical value of EPCs autotransplantation and potential application of a novel strategy of therapy for liver fibrosis that involves combined transplantation of BM-EPCs and BDHSCs.

Research methods

For the treatment of liver fibrosis, BDHSCs, which can promote hepatic cell regeneration, combined with BM-EPCs, which can promote hepatic revascularization, were transplanted into rats with liver fibrosis. The normal functional BM-EPCs and BDHSCs were both successfully obtained from liver fibrosis rats. Tracing analysis was conducted by labeling EPCs with PKH26 in vitro to show EPCs’ location in the liver. After transplantation of BM-EPCs, BDHSCs or both into liver fibrosis rats, the indicators of hepatic neovascularization, liver regeneration, collagen formation, liver fibrosis degree and liver function were observed and detected.

Research results

Normal functional BM-EPCs from liver fibrosis rats were successfully obtained. The co-expression level of CD133 and VEGFR2 was 63.9% ± 2.15%. Transplanted BM-EPCs were located primarily in/near hepatic sinusoids. The combined transplantation of BM-EPCs and BDHSCs promoted hepatic neovascularization, liver regeneration and liver function, and decreased collagen formation and liver fibrosis degree.

Research conclusions

This study demonstrated that it was feasible to obtain normal BM-EPCs “filtered” by in vivo pathological environment from bone marrow of a liver fibrosis rat model. The combined transplantation of BM-EPCs and BDHSCs was performed in order to achieve the dual effects of hepatic neovascularization and liver regeneration for liver fibrosis. The combined transplantation exhibited maximal therapeutic effect compared to that of transplantation of BM-EPCs or BDHSCs alone. These findings highlight the clinical value of EPCs autotransplantation and the potential application of a novel strategy of therapy for liver fibrosis that involves combined transplantation of BM-EPCs and BDHSCs.

Research perspectives

Our research is still at the stage of animal experiments. Further studies are needed to explore the reciprocal mechanism of BM-EPCs and BDHSCs in liver fibrosis. Clinical experiments should be carry out gradually. In addition, whether BM-EPCs might promote tumor angiogenesis and cause potential tumor growth in the process of treating liver fibrosis should also be evaluated in further study.