Human umbilical cord mesenchymal stem cells alleviated TNBS-induced colitis in mice by restoring the balance of intestinal microbes and immunoregulation.

Abstract

AIMS:

Human umbilical cord mesenchymal stem cells (HUMSCs) have been documented to be effective for several immune disorders including inflammatory bowel diseases (IBD). However, it remains unclear how HUMSCs function in regulating immune responses and intestinal flora in the trinitrobenzene sulfonic acid (TNBS)-induced IBD model.

MATERIALS AND METHODS:

We assessed the regulatory effects of HUMSCs on the gut microbiota, T lymphocyte subpopulations and related immune cytokines in the TNBS-induced IBD model. The mice were divided into the normal, TNBS, and HUMSC-treated groups. The effect of HUMSCs was evaluated by Hematoxylin and Eosin (H&E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Metagenomics Illumina sequencing was conducted for fecal samples.

KEY FINDINGS:

We demonstrated that the disease symptoms and pathological changes in the colon tissues of TNBS-induced colitis mice were dramatically ameliorated by HUMSCs, which improved the gut microbiota and rebalanced the immune system, increasing the abundance of healthy bacteria (such as Lactobacillus murinus and Lactobacillus johnsonii), the Firmicutes/Bacteroidetes ratio, and the proportion of Tregs; the Th1/Th17 ratio was decreased. Consistently, the expression levels of IFN-γ and IL-17 were significantly decreased, and transforming growth factor-β1 (TGF-β1) levels were significantly increased in the plasma of colitis mice HUMSC injection.

SIGNIFICANCE:

Our experiment revealed that HUMSCs mitigate acute colitis by regulating the rebalance of Th1/Th17/Treg cells and related cytokines and remodeling the gut microbiota, providing potential future therapeutic targets in IBD.

• Authors: Yanxia Fu, Chen Zhang, Hui Xie, Zisheng Wu, Yurong Tao, Ziyu Wang, Meng Gu, Panjian Wei, Shuye Lin, Ruoran Li, Yuqi He, Jianqiu Sheng, Junfeng Xu, Jinghui Wang, Yuanming Pan
• Journal: Life sciences (Life Sci) Vol. 334 Pg. 122189 (Dec 01 2023) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 37865178 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• Trinitrobenzenesulfonic Acid
• Cytokines

Topics

• Humans
• Mice
• Animals
• Trinitrobenzenesulfonic Acid (toxicity)
• Colitis (chemically induced, therapy)
• Cytokines (metabolism)
• Inflammatory Bowel Diseases (chemically induced, therapy)
• T-Lymphocytes, Regulatory
• Immunity
• Mesenchymal Stem Cells (metabolism)
• Umbilical Cord (metabolism)
• Disease Models, Animal