Uncovering the bequeathing potential of Apoptotic Mesenchymal Stem Cells via small Extracellular Vesicles for its enhanced immunomodulatory ability

Abstract

AbstractSmall Extracellular Vesicles (sEVs) derived from Mesenchymal Stem Cells (MSCs) have emerged as a promising avenue for cell-free therapeutics in regenerative medicine. These vesicles, endowed with regenerative cargo inherited from their parent cells, have attracted attention for their role in immunomodulation and ROS alleviation. Notably, the deliberate induction of apoptosis in MSCs prior to Extracellular Vesicles (EVs) isolation has been identified as a strategy to augment the regenerative capabilities of MSCs-EVs, as certain reports have suggested that MSCs undergo apoptosis to exert their therapeutic effect post-transplantation. Moreover, selecting an optimal tissue source for deriving MSC-sEVs is equally crucial to ensure consistent and improved clinical outcomes.Multiple attributes of MSCs like their antioxidant, Immunomodulatory & regenerative properties make them particularly appealing for clinical studies, wherein mechanisms such as paracrine secretions and efferocytosis play pivotal roles. This investigation meticulously explores the comparative immunomodulatory & antioxidant capabilities of Apoptotic sEVs (Apo-sEVs) with Viable sEVs (V-sEVs) obtained from both Bone Marrow (BM) and Wharton’s Jelly (WJ)-derived MSCs, using anin vitroliver injury model. The findings from the present study contribute valuable insights into the comparative efficacy of Apo-sEVs and V-sEVs. This will aid in addressing a critical gap in understanding the role of apoptosis in enhancing the reparative capability of MSCs-sEVs. It also aims to shed light on the optimal source of MSCs for generating Apo-sEVs in translational applications.GRAPHICAL ABSTARCT