What are possible mechanisms that stem cell therapy use to improve metabolic dysfunction in the body?

Adipose-derived stem cells (ADSCs) may improve obesity through multiple mechanisms, primarily by modulating inflammation, enhancing metabolism, and promoting tissue repair. Although clinical research is still being done and there are no clear evidence of what kind of mechanisms are truly in effect, we can guess on the possible ways.

Here’s how ADSCs may be able to help combat obesity:

1. Anti-Inflammatory Effects

• Regulating Macrophage Polarization: ADSCs promote a shift from pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages in adipose tissue. This reduces chronic inflammation, which is a key contributor to obesity-related metabolic dysfunction.
• Secreting Anti-Inflammatory Cytokines: ADSCs release IL-10, TGF-β, and other factors that suppress pro-inflammatory cytokines like TNF-α and IL-6, improving insulin sensitivity.

2. Promoting Browning of White Adipose Tissue (WAT)

• Enhancing Thermogenesis: ADSCs can differentiate into beige adipocytes, which have higher mitochondrial activity and increase energy expenditure. This helps reduce fat accumulation.
• Increasing UCP1 Expression: ADSC-secreted exosomes and paracrine factors upregulate uncoupling protein 1 (UCP1) in adipocytes, stimulating fat burning.

3. Improving Insulin Sensitivity and Glucose Metabolism

• Enhancing Insulin Signaling: ADSCs release adiponectin and other insulin-sensitizing factors that improve glucose uptake by skeletal muscle and adipose tissue.
• Reducing Lipotoxicity: By promoting fatty acid oxidation, ADSCs help decrease lipid accumulation in non-adipose tissues, preventing insulin resistance.

4. Regenerating and Remodeling Adipose Tissue

• Inhibiting Fibrosis: ADSCs secrete matrix metalloproteinases (MMPs) that reduce extracellular matrix stiffness, preventing dysfunctional adipose tissue remodeling.
• Enhancing Angiogenesis: ADSCs release VEGF and other growth factors to improve blood supply in adipose tissue, preventing hypoxia-induced inflammation.

5. Modulating Gut Microbiota

• Restoring Microbial Balance: ADSCs may influence gut microbiota composition, promoting beneficial bacteria that contribute to weight loss and metabolic health.

6. Affecting Appetite Regulation

• Interacting with the Hypothalamus: ADSCs may secrete factors that influence appetite-related hormones like leptin and ghrelin, helping to regulate food intake.

Conclusion

ADSCs have much potential to improve obesity by reducing inflammation, promoting fat burning, enhancing insulin sensitivity, and remodeling adipose tissue. Their regenerative and immunomodulatory properties make them a promising therapeutic tool for obesity and metabolic disorders.