Cell-free adipose tissue-derived stem cell extracts mediate immunosuppression of lymphocyte via cell cycle arrest

Cell-free mesenchymal stem cell products have shown promise in reducing inflammation, alleviating tissue degeneration, and regulating immune responses. A recent study has reported that adipose tissue-derived stem cell (ADSC) extract possesses immunomodulatory capacity. However, its comparative efficacy against other cell-free products is not well documented. Nevertheless, the underlying mechanism of ADSC extract is under intense investigation. We determined the immunosuppressive efficiency of ADSC extract and ADSC-concentrated conditioned medium (CCM) on T cell proliferation, T regulatory cell expansion, and T cell cycle progression. In addition, the comparative cytokine profiles of ADSC extract and ADSC-CCM were investigated by cytokine array analysis. The ADSC extracts were superior in inhibiting T cell proliferation, promoting T regulatory cell expansion, and inducing activated T cell arrest at G0/G1 phase compared with ADSC-CCM. The inhibitory effect of ADSC extract on T cell proliferation was partly associated with control of cell cycle progression but not apoptosis induction. A halt in cell cycle progression of activated T lymphocyte after ADSC extract exposure was mediated via p21 and p27 activation. The cytokine profiling demonstrated that there were distinct patterns of immunoregulatory components in ADSC extract and ADSC-CCM, likely associated with their differing in immunoregulatory actions. The marked expression of TGF-β1 and IL-10 in the composition of ADSC extract implied their key roles in mediating immunosuppressive actions. IL-10 and TGF-β1 neutralization partly abrogated immunosuppressive capacities of ADSC extract. Together, ADSC extract may serve as an alternative source of immunomodulatory mediators with potential for development as cell-free products for therapeutic use.