Mesenchymal Stromal Cells as Modulators of Chronic Inflammation, Inflammaging, and Age-Related Disease: A Systematic Review

<title>Abstract</title> <p>Background Chronic low-grade inflammation is widely recognized as a central biological driver of aging and many age-related diseases. This persistent inflammatory state, often described as inflammaging(definition), contributes to the development of cardiovascular disease, metabolic disorders, neurodegenerative conditions, and musculoskeletal degeneration. Mesenchymal stromal cells (MSCs) possess immunomodulatory properties that may influence inflammatory signaling pathways and support tissue repair. Objective This systematic review evaluated current preclinical and clinical evidence regarding the effects of mesenchymal stromal cells on inflammatory biomarkers and immune signaling pathways associated with chronic inflammation and inflammaging. Methods A systematic literature search was conducted across PubMed, Embase, Scopus, Web of Science, and the Cochrane Library in accordance with PRISMA 2020 guidelines. Studies evaluating MSC therapy and reporting inflammatory biomarker outcomes were included. Data extraction included study design, MSC source, route of administration, disease model or patient population, inflammatory biomarkers evaluated, and reported clinical outcomes. Results Included studies consistently demonstrated that MSC therapies modulate inflammatory signaling through multiple mechanisms, including suppression of pro-inflammatory cytokines and enhancement of anti-inflammatory mediators. Reductions in biomarkers such as IL-6, TNF-α, IL-1β, and C-reactive protein were frequently observed following MSC therapy. Several studies also reported increased levels of anti-inflammatory cytokines such as IL-10. Improvements in clinical outcomes across various disease models were frequently associated with these immunomodulatory effects. Conclusion Current evidence suggests that mesenchymal stromal cells exert meaningful immunomodulatory effects that may influence chronic inflammatory pathways associated with aging. These findings support further investigation of MSC-based therapies as potential strategies for addressing inflammaging and age-related disease.</p>