MIR-29A PLAYS A CRUCIAL ROLE IN THE THERAPEUTIC EFFECT OF ASC-DERIVED EXTRACELLULAR VESICLES IN SYSTEMIC SCLEROSIS
- Alexandre MARIA, France
Abstract
Background and Aims
Systemic sclerosis (SSc) is a life-threatening autoimmune disease with unmet medical need, where mesenchymal stromal/stem cells (MSCs) may represent a promising therapeutic approach. MSCs act primarily through the secretion of soluble factors released within extracellular vesicles (EVs). Here, we investigated the effect of adipose-derived mesenchymal stromal cells (ASCs)-EV in the murine model of hypochlorite (HOCl)-induced SSc and the role of miR-29a, a known anti-fibrotic factor.
Methods
HOCl-SSc was induced by 6-weeks daily intradermal HOCl injections. EV were isolated from ASCs. Groups of 8 mice were treated at day 21 with one intravenous injection of PBS, 2.5x105ASCs, 4x107EV isolated from naive ASCs or ASCs transfected by miR-29a inhibitor or control inhibitor. Skin thickness was measured weekly and skin and lung samples were recovered at euthanasia.
Results
EV significantly reduced skin thickness and the expression levels of fibrotic and inflammatory markers in skin and lung tissues, while increasing the expression of extracellular matrix remodeling markers. Injection of ASCs transfected with miR-29a inhibitor in the murine model of SSc resulted in the loss of their therapeutic effect. Interestingly, the injection of EVs isolated from ASCs transfected with miR-29a inhibitor was not able to reduce the clinical symptoms of SSc.
Conclusions
Systemic injection of ASC-derived EVs exerted a similar therapeutic effect as whole ASCs in the murine model of SSc. This effect was, at least in part, mediated by miR-29a.