Research Paper Volume 12, Issue 21 pp 21660—21673

Human mesenchymal stem cells treatment improved hepatic lesions and reversed gut microbiome disorder in non-alcoholic steatohepatitis

Zhiyu Yang1,2, *, , Qiaoyun Xia1, *, , Di Lu1,2, *, , Han Yue3, , Jianmin Zhang1, , Yalong Li3, , Bingyong Zhang1, , Xiuling Li1, , Mingbo Cao1, ,

  • 1 Department of Gastroenterology, Henan Provincial People’s Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan, China
  • 2 Microbiology Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan, China
  • 3 Stem Cell Research Center, Henan Key Laboratory of Stem Cell Differentiation and Modification Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, Henan, China
* Equal contribution

Received: June 19, 2020       Accepted: August 1, 2020       Published: November 8, 2020      

https://doi.org/10.18632/aging.103962
How to Cite

Copyright: © 2020 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Effective therapies for non-alcoholic steatohepatitis (NASH) are urgently needed. We investigated the effect of human mesenchymal stem cells (hMSCs) on the intestinal flora in NASH treatment. We isolated the hMSCs from the umbilical cords and divided male C57BL/6 mice into three groups, namely, chow, methionine–choline-deficient (MCD), and MCD+hMSCs. After collecting the feces and liver of the mice, we evaluated the histological changes in the liver and measured the inflammatory and fibrogenesis cytokines. Fecal microbiome and metabolome were analyzed using 16S rRNA gene sequencing analyses. The hMSCs treatment could alleviate hepatic steatosis, inflammation and fibrosis induced by MCD diet. It could also reverse the microbiome and metabolome disorders in the NASH model. Correlation analysis of the interaction among bacteria amplified the effects of the bacteria in host. In conclusion, hMSCs treatment could improve NASH-related lesions and reverse gut microbiome and metabolome disorder in NASH.

Abbreviations

MCD: Methionine–choline-deficient diet; hMSCs: Human mesenchymal stem cells; NASH: Non-alcoholic steatohepatitis; NAFLD: Non-alcoholic fatty liver disease; LPS: Lipopolysaccharides; SCFAs: Short chain fatty acids; PCoA: Principal coordinate analysis; TNF-a: Tumor necrosis factor-a; CXCL-2: Chemokine(C-X-C motif) ligand 2; a-SMA: Alpha-smooth muscle actin; CTGF: Connective tissue growth factor; KEGG: Kyoto encyclopedia of Genes and Genomes; ANOVA: One-way analysis of variance; HE: Hematoxylin-eosin staining; qPCR: Quantitative polymerase chain reaction; FITC: Fluorescein isothiocyanate; PE: Phycoerythrin; APC: Allophycocyanin.