English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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 phenotype, coupled with elevated serum IL-10 levels. In vivo blockade of IL-10 blunted the effects of UC-MSCs on obese mice. Furthermore, UC-MSCs overwhelmingly homed to the spleen, and the ability of UC-MSCs to elevate serum IL-10 levels and alleviate insulin resistance was impaired in the absence of the spleen. Further in vivo and in vitro studies revealed that UC-MSCs promoted the capacity of regulatory T cells (Treg cells) to produce IL-10 in the spleen. Conclusions Our results demonstrated that UC-MSCs elevated serum IL-10 levels and subsequently promoted macrophage polarization, leading to alleviation of insulin resistance in EAT. The underlying mechanism was that UC-MSCs improved the capacity of Treg cells to produce IL-10 in the spleen. Our findings indicated that the spleen played a critical role in amplifying MSC-mediated immunomodulatory effects, which may contribute to maximizing MSC efficacy in clinical applications in the future.

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