MSC–DERIVED EXTRACELLULAR VESICLES
How MSCs exert their beneficial effect in tissue repair remains elusive. However, increasing evidence suggests that their therapeutic efficacy is not dependent on MSCs engraftment at the site of injury or their differentiation capability, but it rather relies on secreted mediators. Recent studies have demonstrated that MSC-derived extracellular vesicles (MSC-EVs) such as exosomes exert beneficial effects in different disease models. Exosomes are 40-140nm secreted vesicles that are formed by the invagination of the limiting membrane of the multivesicular bodies (MVBs), which are part of cellular endo-lysosomal system. Upon fusion of MVBs with the plasma membrane, exosomes are released into the extracellular environment. Another prominent EVs entity are microvesicles (MVs; 100-1000 nm), which bud off the plasma membrane. All cells are capable of EVs/exosome secretion and they are also found in all body fluids. EVs exert many of their functions as an intercellular shuttle, carrying cargo such as protein and RNA to be transferred from one cell to another.
We would like to understand how MSC use EVs to communicate with cells from different injured tissues. We study this in context of diseases such as osteoarthritis, graft versus host disease, inherited metabolic disorders and neurodegenerative disorders.
CROSSTALK BETWEEN EVs AND AUTOPHAGY
Autophagy is an essential cellular homeostasis mechanism whereby cellular organelles and macromolecules are recycled to maintain cellular metabolism. The autophagy pathway is integrated with multiple signal transduction pathways that respond to nutrient supply, energy balance, cytokines, and growth factors. It is an important regulator of mammalian development under both physiological and pathological conditions. Autophagy also plays a significant role in stem cell maintenance, by clearing harmful substances which could otherwise cause the cells to lose their pluripotency or undergo cell death. Extracellular vesicles also contribute to the selective secretion of harmful/damaged proteins and RNAs and the maintenance of cellular homeostasis. And growing evidence indicates the molecular and functional crosstalk between extracellular vesicles release and autophagy pathways.
We study how this interaction between EV release and autophagy regulates MSC biology and their regenerative potential.