WHY MICROVESICLES AND EXOSOMES
The biological effector of mesenchymal stem/stromal cells is their secretome, which is composed of a heterogeneous pool of bioactive molecules, partially enclosed in extracellular vesicles, namely microvesicles and exosomes.
Therefore, the secretome, including microvesicles and exosomes, is an alternative to mesenchymal stem cell therapy. The secretome can be considered as a protein-based biotechnological product, it is safer compared with living/cycling cells, it presents virtually lower tumorigenic risk, and it can be handled, stored and sterilized as an Active Pharmaceutical/Principle Ingredient.
Extracellular vesicles present structural and technological analogies with liposomes, and can be considered “ideal next generation drug delivery system”, retaining several desirable features including cytocompatibility, biocompatibility, intrinsic targeting and high bloodstream stability.
Extracellular vesicles can encapsulate both hydrophilic and lipophilic therapeutics and deliver them even through “hard to cross barriers” such as the Blood Brain Barrier, avoiding phagocytosis or degradation mediated by macrophages. Moreover extracellular vesicles preserve some of their parental cell features such as homing (ability to reach inflamed and damaged tissues Figure 1), to prolong the release of encapsulated drugs, immunomodulatory and regenerative potential.
Figure 1 - Hypothesis of the mesenchymal stem cell homing mechanism: A) direct cell-to-cell contact: mesenchymal stem cells adhere and cross the endothelial membrane by expressing a restricted set of molecules, reaching the inflamed/damaged site; B) cell-secreted factors (Secretome) able to cross the endothelial membrane, entering the bloodstream and finally reaching the injured cells.