Therapeutic Efficacy of Adipose-Derived Stem Cell Extracellular Vesicles in Autoimmune and Inflammatory Diseases: A Systematic Review

Abstract

Background: Adipose-derived stem cells (ADSCs) and their extracellular vesicles (ADSC-EVs) have become fundamental components in the fields of regenerative medicine and immunomodulation. This review evaluates existing preclinical and clinical evidence on the role of ADSC-EVs in modulating innate and adaptive immune responses to mitigate inflammatory and autoimmune conditions. Autoimmune and chronic inflammatory disorders, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), and multiple sclerosis (MS), are characterized by immune system dysregulation, a failure of self-tolerance, and pathological cytokine signaling. ADSC-EV-based cell-free therapies represent a compelling immunomodulatory approach, delivering the regenerative advantages of mesenchymal stem cells while circumventing the risks associated with cellular transplantation.
Objectives: This systematic review synthesizes preclinical and clinical research on how ADSC-EVs modulate innate and adaptive immunity to treat autoimmune and inflammatory conditions.
Methods: Following PRISMA protocols, we conducted systematic searches in PubMed, Embase, and PMC, focusing on studies concerning ADSC-EVs, immunomodulation, macrophage polarization, and T-cell regulation.
Findings: From 70 initially screened records, 47 met the final inclusion criteria. ADSC-EVs consistently demonstrate potent anti-inflammatory and immunoregulatory capabilities. Their cargo comprising specialized microRNAs (e.g., miR-146a, miR-21), functional proteins, and lipids targets key immune pathways (such as NF- kappa B and STAT3 signaling) to suppress hyperactive inflammation.
Conclusion: ADSC-EVs represent a promising, cell-free frontier in immunotherapy. By orchestrating macrophage polarization, expanding regulatory T cells, and suppressing destructive cytokine storms, they offer broad therapeutic utility for inflammatory and immune-mediated diseases.