Effect of CXCR3/HO-1 genes modified bone marrow mesenchymal stem cells on small bowel transplant rejection

doi:10.3748/wjg.v23.i22.4016

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World Journal of Gastroenterology

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1007-9327

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Basic Study

World J Gastroenterol. Jun 14, 2017; 23(22): 4016-4038
Published online Jun 14, 2017. doi: 10.3748/wjg.v23.i22.4016

Effect of CXCR3/HO-1 genes modified bone marrow mesenchymal stem cells on small bowel transplant rejection

Ming-Li Yin, Hong-Li Song, Yang Yang, Wei-Ping Zheng, Tao Liu, Zhong-Yang Shen

Ming-Li Yin, Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin 300070, China

Hong-Li Song, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin Clinical Research Center for Organ Transplantation and Tianjin Key Laboratory of Organ Transplantation, Tianjin 300192, China

Yang Yang, Wei-Ping Zheng, Zhong-Yang Shen, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China

Tao Liu, Tianjin First Central Hospital and Key Laboratory of Emergency and Care Medicine of Ministry of Health, Tianjin 300192, China

Author contributions: Yin ML, Song HL and Yang Y performed the research, analyzed the data, and wrote and revised the paper; Yin ML, Yang Y, Zheng WP and Liu T performed the research; Song HL participated in research design; Shen ZY designed the research and participated in the revision of the paper; all authors have read and approved the final manuscript.

Supported by The National Natural Science Foundation of China, No. 81670574, No. 81441022 and No. 81270528; The Natural Science Foundation of Tianjin, China, No. 08JCYBJC08400, No. 11JCZDJC27800 and No. 12JCZDJC25200; and The Technology Foundation of the Health Bureau of Tianjin, China, No. 2011KY11.

Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Tianjin First Central Hospital.

Institutional animal care and use committee statement: All experiment on animals were performed in accordance with the “Guide for the Care and Use of Laboratory Animals” (National Institutes of Health, 8^th ed. 2011). All procedures involving animals were reviewed and approved by the Animal Care and Research Committee of Tianjin First Central Hospital.

Conflict-of-interest statement: The authors declare no potential conflict of interest for this paper.

Data sharing statement: No additional data are available.

Correspondence to: Zhong-Yang Shen, MD, PhD, Professor, Department of Organ Transplantation, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin 300192, China. shenzhy@tmu.edu.cn

Telephone: +86-22-2362698 Fax: +86-22-2362698

Received: January 5, 2017
Peer-review started: January 9, 2017
First decision: March 3, 2017
Revised: March 20, 2017
Accepted: May 4, 2017
Article in press: May 4, 2017
Published online: June 14, 2017
Processing time: 159 Days and 14.5 Hours

Core Tip

Core tip: In this paper, transplant recipient rats were pretreated with bone marrow mesenchymal stem cells (BMMSCs) in advance, and these rats were in a compromised immune state. CXCR3/HO-1 gene modified BMMSCs were injected into recipient rats after small bowel transplantation. The survival time of these rats was significantly prolonged; the number of cells that underwent apoptosis was significantly lower in the CXCR3/HO-1 modified BMMSCs group compared with rats from the HO-1 gene modified BMMSCs group, the native BMMSCs group, and the NS group. Furthermore, the percentage of regulatory T cells was significantly increased. Proinflammatory cytokines (IL-2, IL-6, IL-17, IFN-γ, and TNF-α) were significantly reduced, while anti-inflammatory cytokines (IL-10 and TGF-β) were significantly increased. Our data suggest that BMMSCs modified with the CXCR3 and HO-1 gene can reduce rejection of the small intestine more effectively than HO-1 modified BMMSCs and native BMMSCs.