Fig. 3: Apoptosis and apoEV contribution to the therapeutic effects of MSCs.
From: Emerging understanding of apoptosis in mediating mesenchymal stem cell therapy
Under the multiple exogenous apoptotic stimuli, MSCs in culture can be induced to apoptosis to form apoptotic cells and apoEVs, which are collected and infused to various disease models. ApoEVs transplanted or released by infused apoptotic cells have been demonstrated to carry bioactive proteins and miRNAs to recipient cells for tissue homeostasis maintenance and immunoregulation. For examples, infused apoptotic cells and apoEVs are traced in lung and engulfed by phagocytes, which possess potent capacities of immunomodulation in inflammatory insults. ApoEVs regulate the number of immune cells and promote macrophage M2 polarization in multiple diseases including acute kidney injury, the colitis, allergic lung inflammation, and cutaneous wound healing. Apoptotic cells and apoEVs can also be engulfed by endogenous MSCs and endothelial cells, contributing to the rescue of impaired stem cells and tissue regeneration. While the therapeutic effects of apoptotic cells and apoEVs are remarkable, the mechanisms underlying molecular delivery and potential interplays between donors and recipients remain elusive.
