Adipose-Derived Mesenchymal Stem Cells from Arthritis Patients: Differential Modulation of CD4⁺ T Cell Activation and Cytokine Production.

Abstract

BACKGROUND Adipose-derived stem cells (ASCs) from intra-articular adipose tissue of osteoarthritis (OA) and rheumatoid arthritis (RA) patients similarly regulate the proliferation of activated CD4⁺ T lymphocytes and exhibit comparable differentiation potential. This study aimed to assess the impact of ASCs from RA patients on CD4⁺ T cell activation and differentiation into Th17 and T regulatory (Treg) cells. MATERIAL AND METHODS Intra-articular adipose tissue samples were obtained from patients with RA and OA, who underwent knee replacement surgery. ASCs were isolated and cultured either with isolated CD4⁺ cells or with peripheral blood mononuclear cells. After culture, CD4⁺ T cell phenotype was evaluated by flow cytometry, and cytokine concentrations in culture supernatants were analyzed via ELISA. Blocking experiments were conducted to identify the soluble agents responsible for the immunomodulatory effects of ASCs. RESULTS RA- and OA-derived ASCs effectively modulated CD25 and CD69 expression on CD4⁺ cells. RA-derived ASCs failed to induce Tregs, decreased HLA-DR expression, and increased IL-35 production. RA- and OA-derived ASCs reduced TNF and IFN-γ production but increased IL-17 production. The immunomodulatory activities of ASCs were linked to the kynurenine pathway and prostaglandin E2. CONCLUSIONS This study indicates that ASCs modulate the phenotype of CD4⁺ T cells and influence the production of both pro-inflammatory and anti-inflammatory cytokines. However, ASCs from RA patients appear to have impaired immunomodulatory abilities, raising concerns about their therapeutic potential. Further research is needed to enhance our understanding of ASCs biology and their therapeutic utility.