Inflammation Accelerates Mesenchymal Stem Cell Aging

Chronic inflammation disrupts tissue function throughout the body, contributing to the onset and progression of age-related conditions. One of the wide variety of ways in which this happens is via detrimental changes in stem cell populations and their activities. Researchers here focus down on mesenchymal stem cells in bone marrow as one example of many that might be considered. That senescent cells act to maintain an inflammatory environment is one of the reasons why removal of senescent cells produces profound and rapid rejuvenation in animal studies. More methods of cleanly reducing chronic inflammation with minimal side-effects are very much needed, a necessary part of the toolkit of rejuvenation therapies presently under development.

Mesenchymal stem cell (MSC) senescence is considered a contributing factor in aging-related diseases. We investigated the influence of the inflammatory microenvironment on bone marrow mesenchymal stem cells (BMSCs) under aging conditions and the underlying mechanism to provide new ideas for stem cell therapy for age-related osteoporosis. The BMSCs were cultured until passage 3 (P3) (young group) and passage 10 (P10) (aging group) in vitro. The supernatant was collected as the conditioned medium (CM). The young BMSCs were cultured in the CM of P3 or P10 cells. The effects of CM from different groups on the aging and stemness of the young BMSCs were examined. An inflammation assay was conducted on serum extracts from young (aged 8 weeks) and old (aged 78 weeks) mice, and differentially expressed factors were screened out.

We discovered that the CM from senescent MSCs changed the physiology of young BMSCs. Systemic inflammatory microenvironments changed with age in the mice. In particular, the pro-inflammatory cytokine IL-6 increased, and the anti-inflammatory cytokine IL-10 decreased. The underlying mechanism was investigated, and there was a change in the JAK-STAT signaling pathway, which is closely related to IL-6 and IL-10. Collectively, our results demonstrated that the age-related inflammatory microenvironment has a significant effect on the biological functions of BMSCs. Targeted reversal of this inflammatory environment may provide a new strategy for stem cell therapy to treat aging-related skeletal diseases.


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