(M-493) The Impact of Extracellular-Vesicles derived under Hypoxic and Normoxic Conditions on Inflammation and Muscle Regeneration

A substantial loss of muscle tissue (>20%), termed as a volumetric muscle loss (VML) impairs the ability of skeletal muscle to repair and regenerate itself and leads to persistent inflammation and fibrosis at the injury site. Currently, there is no definitive therapy for VML that can regenerate the lost contractile tissue or restore muscle strength. Mesenchymal stem cells (MSCs) are adult multipotent stem cells that form muscle tissue under specific conditions [1]. Besides muscle tissue formation, MSCs support blood vessel growth, release a variety of growth factors, suppress inflammation and prevent fibrosis. Studies show that MSCs typically don’t survive after transplantation [2, 3]. However, the therapeutic benefits of MSCs may still be realized by relying on their secreted products that are packaged in extracellular vesicles (EVs). These vesicles contain bioactive molecules such as lipids, proteins, mRNAs and microRNAs (miRNAs) unique to the cell of origin [4, 5]. Studies have shown that MSC derived EVs can polarize macrophages towards the anti-inflammatory M2 phenotype, accelerate wound healing and increase tissue regeneration (2). Furthermore, hypoxic preconditioning (HP), a technique that involves exposing cells to a controlled low oxygen environment and has been shown to promote stem cell survival post-transplantation and angiogenesis (3). Our hypothesis is that HP can enhance the release of EVs from MSCs while simultaneously altering their composition to make them anti-inflammatory and pro-repair.