Mesenchymal stem cell-derived secretome and microvesicles as a cell-free therapeutics for neurodegenerative disorders

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that can be isolated from various fetal and adult tissues. Over the fast decades, their multipotency, tissue reparative action, homing ability and immunoregulatory properties raised a great expectation in the field of stem cell and regenerative medicine that is being actively translated in a number of clinical trials worldwide. While MSC-based therapies have proven effectiveness in a numerous experimental models of human diseases and clinical studies including neurodegenerative disorders, there are accumulating evidences suggesting that the observed therapeutic effects in tissue regeneration is likely due to the paracrine actions of MSCs. Indeed, MSCs secrete trophic factors and cytokines (secretome) that have therapeutic relevance for the neurogenic, neuroprotective, angiogenic and anti-inflammatory/immunoregulatory activities. In addition, extracellular vesicles, such as microvesicles and exosomes, are proposed as key mediators of information transfer between different cells for tissue repair and regeneration. Although the underlying mechanism(s) of reparative action is not clear, evidences suggest that MSC secretome and microvesicles can recapitulate the beneficial effects as their cellular counterparts in tissue regeneration. Thus, secretome and microvesicles represent a promising candidate for a novel cell-free therapy for neurodegenerative diseases that has many advantages in overcoming the limitations and risks associated with the cell-based therapeutics.ope