Nestin+ Peyer's patch resident MSCs enhance healing of inflammatory bowel disease through IL‐22‐mediated intestinal epithelial repair

• Published in: Cell proliferation 2023-02, Vol.56 (2), p.e13363-n/a
• Main Authors: Chen, Jieying, Huang, Jing, Shi, Jiahao, Li, Minrong, Zhao, Erming, Li, Gang, Chen, Xiaoyong, Wang, Tao, Li, Qiaojia, Li, Weiqiang, Ma, Jianping, Mao, Wenzhe, Fang, Rui, Hao, Jiang, Huang, Weijun, Xiang, Andy Peng, Zhang, Xiaoran
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Bone marrow; Bone Marrow Cells; Cell proliferation; Effectiveness; Gastrointestinal system; Gastrointestinal tract; Gene expression; Homeostasis; Immunomodulation; Immunoregulation; Inflammation; Inflammatory bowel disease; Inflammatory Bowel Diseases; Interleukin 22; Intestine; Intestines; Laboratories; Lymphocytes; Lymphocytes T; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mesenchyme; Mice; Mice, Transgenic; Nestin; Original; Signs and symptoms; Software; Stromal cells; Transgenic mice
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.13363

Inflammatory bowel disease (IBD) is a chronic condition characterized by gastrointestinal tract inflammation and still lacks satisfactory treatments. Mesenchymal stromal cells (MSCs) show promising potential for treating IBD, but their therapeutic efficacy varies depending on the tissue of origin. We aim to investigate whether intestine Peyer's patch (PP)‐derived MSCs have superior immunomodulatory effects on T cells and better therapeutic effects on IBD compared with bone marrow‐derived MSCs. We isolated PPs‐derived Nestin+ MSCs (MSCsPP) and bone marrow‐derived Nestin+ MSCs (MSCsBM) from Nestin‐GFP transgenic mice to explore their curative effects on murine IBD model. Moreover, we tested the effects of IL‐22 knockdown and IL‐22 overexpression on the therapeutic efficacy of MSCsPP and MSCsBM in murine IBD, respectively. We demonstrated that Nestin+ cells derived from murine PPs exhibit MSC‐like biological characteristics. Compared with MSCsBM, MSCsPP possess enhanced immunoregulatory ability to suppress T cell proliferation and inflammatory cytokine production. Moreover, we observed that MSCsPP exhibited greater therapeutic efficacy than MSCsBM in murine IBD models. Interestingly, IL‐22, which was highly expressed in MSCsPP, could alleviate the severity of the intestinal inflammation, while knockdown IL‐22 of MSCsPP remarkably weakened the therapeutic effects. More importantly, IL‐22 overexpressing MSCsBM could significantly improve the symptoms of murine IBD models. This study systemically demonstrated that murine MSCsPP have a prominent advantage in murine IBD treatment, partly through IL‐22. We isolated bone marrow‐derived Nestin+ cells (MSCsBM) and Peyer's patches‐derived Nestin+ cells (MSCsPP) with Nestin‐GFP transgenic mice. To systematically explore their properties, we analysed their proliferation abilities, differentiative potentials, especially immunoregulatory capabilities, and verified the feature using an inflammatory bowel disease (IBD) murine model. The results indicated that MSCsPP exhibited far more superior efficacy than MSCsBM in the treatment of IBD, mainly due to their high expression of IL‐22.