Human umbilical cord-derived mesenchymal stem cells alleviate insulin resistance in diet-induced obese mice via an interaction with splenocytes

作者：Jing Xue, Jieqing Gao, Yulin Gu, Aihong Wang, Songyan Yu, Bing Li, Yaqi Yin, Jie Wang, Wanlu Su, Haixia Zhang, Weizheng Ren, Weijun Gu, Zhaohui Lv, Yiming Mu, Yu Cheng · 发表于：Stem Cell Research & Therapy · 年份：2022 · DOI：10.1186/s13287-022-02791-6 · 被引用次数：17 · 研究领域：Mesenchymal stem cell research、Adipokines, Inflammation, and Metabolic Diseases、Spinal Cord Injury Research

BACKGROUND: Previous research has demonstrated that the spleen plays an important role in mesenchymal stem cell (MSC)-mediated alleviation of acute inflammation, as MSC infusion increases the spleen-derived anti-inflammatory cytokine interleukin 10 (IL-10) levels. However, studies on splenic involvement in MSC-induced protection against chronic inflammatory diseases are limited. Obesity is characterized by chronic low-grade inflammation, a key driver of insulin resistance. This study aims to evaluate the effects of MSCs on obesity-related insulin resistance and explore the underlying mechanism, particularly regarding splenic involvement. METHODS: We induced obesity in mice by feeding them high-fat diets for 20 weeks. Human umbilical cord-derived MSCs (UC-MSCs) were systemically infused into the obese mice once per week for 6 weeks. Systemic glucose metabolic homeostasis and insulin sensitivity in epididymal adipose tissue (EAT) were evaluated. Then, we conducted in vivo blockade of IL-10 during UC-MSC infusion by intraperitoneally administrating an IL-10-neutralizing antibody twice per week. We also investigated the therapeutic effects of UC-MSCs on obese mice after removal of the spleen by splenectomy. RESULTS: UC-MSC infusions improved systemic metabolic homeostasis and alleviated insulin resistance in EAT but elicited no change in weight. Despite rare engraftment of UC-MSCs in EAT, UC-MSC infusions attenuated insulin resistance in EAT by polarizing macrophages into the M2 ...