Senescence of mesenchymal stem cells: implications in extracellular vesicles, miRNAs and their functional and therapeutic potentials

Abstract

Senescence is seen as the cellular counterpart of tissue and biological aging, with irreversible stagnation of cell growth, and changes in function and behavior. Mesenchymal stem cells (MSCs) are one of the key therapeutic tools in regenerative medicine, and their regenerative and therapeutic potential declines significantly with the increasing age of cell donors and prolonged continuous culture in vitro. MicroRNAs (miRNAs) are regarded as important players in regulating the expression and function of multiple genes and pathways. Emerging evidence suggests that extracellular vesicles (EVs) participate in a complex cell senescence network, at least partially by providing certain miRNAs. Therefore, MSC EVs and miRNAs are implicated in not only contributing to but also influenced by MSC senescence. Here, we will provide an overview of the recent results on roles and mechanisms of miRNAs, particularly EV-miRNAs, involved in MSC senescence, and discuss their implications in functional properties and therapeutic efficacy of MSCs and their EVs. Keywords: Extracellular vesicles, microRNAs, mesenchymal stem cells, senescence