Stem cell-derived microvesicles: a cell free therapy approach to the regenerative medicine

Microvesicles (MVs) include a heterogeneous population of vesicles released as exosomes from the endosomal compartment or as shedding vesicles from the cell surface of different cell types. The broad spectrum of biological activities displayed by MVs candidate them to a pivotal role in cell-to-cell communication. It is now recognized that they constitute an integral part of the intercellular microenvironment acting as vehicle for information transfer. After receptorligand interaction with target cells, MVs may directly stimulate the cells or may transfer from the cell of origin various bioactive molecules including membrane receptors, bioactive lipids and proteins. In addition, MVs may induce epigenetic changes in target cells by delivering specific subsets of mRNA and microRNA associated with different cell functions such as differentiation of blood cells, metabolic pathways and modulation of immune response. In vivo, MVs released from mesenchymal stem cells may account for the described paracrine action of these cells in tissue regeneration. A bidirectional exchange of genetic information between stem and injured cells could be envisaged: i) transcripts delivered by MVs from injured cells may reprogram the phenotype of stem cells to acquire specific features of the tissue; ii) transcripts delivered by MVs from stem cells may limit tissue injury and induce cell cycle re-entry of resident cells leading to tissue self-repair. This review presents an overview of the many biological actions of MVs produced by stem cells that may be exploited in regenerative medicine to repair damaged tissues as an alternative to stem cell-based therapy.