Microvesicles and their emerging role in cellular therapies for organ and tissue regeneration

Abstract

Microvesicles (MVs) are small, spherical membrane fragments shed from the cell surface or secreted from the endosomal compartment. MVs released from cells employed in regenerative medicine to rescue damaged tissues seem to play an important and underappreciated role in improving the function of damaged organs. A growing body of evidence suggests that MVs secreted from hematopoietic stem progenitor cells (HSPCs), multipotent stroma cells (MSCs), or cardiac stem cells (CSCs) employed in various treatment strategies in regenerative medicine may: (1) inhibit apoptosis of cells residing in the damaged tissues, (2) stimulate proliferation of cells that survive organ injury, and (3) stimulate vascularization of affected tissues. These proregenerative effects mediated by MVs are explained by the fact that these small, spherical membrane fragments: (1) are enriched in bioactive lipids (e.g., sphingosine-1-phosphate [S1P]), (2) may express antiapoptoic and prostimulatory growth factors or cytokines (e.g., vascular endothelial growth factor [VEGF], stem cell factor [SCF], or stromal derived factor-1 [SDF-1]) on their surface, and (3) may deliver mRNA, regulatory miRNA, and proteins to the damaged tissues that improve overall cell function. Based on these observations, the potential use of MVs, instead of whole cells, has become an exciting new concept in regenerative medicine.