Extracellular Vesicles isolated from mesenchymal stem cell (MSCs) negatively regulates human T cell survival by inducing caspase cascade and inhibiting anti-apoptotic proteins

Objective(s): Extracellular Vesicles (EVs) transports active biomolecules between human many cells. As natural nanoparticles (NP), exosomes (Exo), plays important roles in the diagnosis and also treatment, of human disorders. Recently, it has been exhibited that mesenchymal stem cell (MSC)-derived Exo could regulate immune cells’ biological processes. We evaluated the influence of the MSCs-derived Exo on T cell survival. Methods: Exo were procured from the supernatant of bone marrow (BM)-MSCs. The structure and form of MSC-Exo were investigated using transmission electron microscopy (TEM). Exo markers, CD9 and CD63, were detected by Western blotting. In co-culture condition with MSC-derived Exo, the survivals of T cells were assessed by flow cytometry. Also, the expression levels of the Caspase-3, Caspase-8, Bcl-2 and Mcl-1 were measured by Real-time PCR. Results: MSCs-derived Exo induced apoptosis in human T cells more strongly within 72 hours but not 24 hours of co-culture. Real-time PCR results also showed that Exo co-culture led to down-regulation of Mcl-1, and Bcl-2 while inducing Caspase 3 and 8 expressions at mRNA levels. Conclusions: MSCs-derived Exo could induce apoptosis in T cells and lead to immunomodulation by triggering caspase cascade and also down-regulating anti-apoptotic protein levels.