Zhao LN, Ma SW, Xiao J, Yang LJ, Xu SX, Zhao L. Bone marrow mesenchymal stem cell therapy regulates gut microbiota to improve post-stroke neurological function recovery in rats. World J Stem Cells 2021; 13(12): 1905-1917 [PMID: 35069989 DOI: 10.4252/wjsc.v13.i12.1905]
Corresponding Author of This Article
Lan Zhao, PhD, Research Fellow, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, No. 88 Chang Ling Road, Xi Qing District, Tianjin 300381, China. lanzhao69@163.com
Research Domain of This Article
Neurosciences
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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/
World J Stem Cells. Dec 26, 2021; 13(12): 1905-1917 Published online Dec 26, 2021. doi: 10.4252/wjsc.v13.i12.1905
Bone marrow mesenchymal stem cell therapy regulates gut microbiota to improve post-stroke neurological function recovery in rats
Lin-Na Zhao, Song-Wen Ma, Jie Xiao, Li-Ji Yang, Shi-Xin Xu, Lan Zhao
Lin-Na Zhao, Song-Wen Ma, Jie Xiao, Li-Ji Yang, Shi-Xin Xu, Lan Zhao, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
Lin-Na Zhao, Song-Wen Ma, Jie Xiao, Li-Ji Yang, Shi-Xin Xu, Lan Zhao, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China
Lin-Na Zhao, Shi-Xin Xu, Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300381, China
Author contributions: Zhao LN and Zhao L drafted and wrote the paper; Ma SW and Xiao J performed the experiments; Yang LJ performed the statistical analysis; Xu SX contributed to designing the experiments and revising the article.
Supported byNational Natural Science Foundation of China, No. 81774059 and No. 82074533; Tianjin Natural Science Foundation, No. 19JCZDJC37100.
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 Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (IACUC protocol number: [Protocol No. TCM-LAEC2019038]).
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Data sharing statement: No additional data are available.
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 that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lan Zhao, PhD, Research Fellow, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, No. 88 Chang Ling Road, Xi Qing District, Tianjin 300381, China. lanzhao69@163.com
Received: May 5, 2021 Peer-review started: May 5, 2021 First decision: June 23, 2021 Revised: July 6, 2021 Accepted: December 11, 2021 Article in press: December 11, 2021 Published online: December 26, 2021 Processing time: 233 Days and 23.4 Hours
Abstract
BACKGROUND
As a cellular mode of therapy, bone marrow mesenchymal stem cells (BMSCs) are used to treat stroke. However, their mechanisms in stroke treatment have not been established. Recent evidence suggests that regulation of dysregulated gut flora after stroke affects stroke outcomes.
AIM
To investigate the effects of BMSCs on gut microbiota after ischemic stroke.
METHODS
A total of 30 Sprague-Dawley rats were randomly divided into three groups, including sham operation control group, transient middle cerebral artery occlusion (MCAO) group, and MCAO with BMSC treatment group. The modified Neurological Severity Score (mNSS), beam walking test, and Morris water maze test were used to evaluate neurological function recovery after BMSC transplantation. Nissl staining was performed to elucidate on the pathology of nerve cells in the hippocampus. Feces from each group of rats were collected and analyzed by 16s rDNA sequencing.
RESULTS
BMSC transplantation significantly reduced mNSS (P < 0.01). Rats performed better in the beam walking test in the BMSC group than in the MCAO group (P < 0.01). The Morris water maze test revealed that the BMSC treatment group exhibited a significant improvement in learning and memory. Nissl staining for neuronal damage assessment after stroke showed that in the BMSC group, cells were orderly arranged with significantly reduced necrosis. Moreover, BMSCs regulated microbial structure composition. In rats treated with BMSCs, the abundance of potential short-chain fatty acid producing bacteria and Lactobacillus was increased.
CONCLUSION
BMSC transplantation is a potential therapeutic option for ischemic stroke, and it promotes neurological functions by regulating gut microbiota dysbiosis.
Core Tip: Bone marrow mesenchymal stem cell (BMSC) transplantation provides a novel approach for ischemic stroke therapy. Studies on the “gut-brain axis” indicate that gut microbiota dysbiosis affects stroke prognosis. We investigated the interactions between BMSCs and gut microbiota. Our findings indicate that the therapeutic mechanism of BMSCs on ischemic stroke treatment may involve the regulation of microbiome structure and function.
