Mesenchymal Stem Cell-Derived Extracellular Vesicles: Opportunities and Challenges for Clinical Translation

Abstract

Extracellular vesicles (EVs), including exosomes and microvesicles, derived from mesenchymal stem/stromal cells (MSCs) exert similar effects as their parental cells, and are of interest for various therapeutic applications. EVs can act through uptake by the target cells followed by release of their cargo inside the cytoplasm, or through interaction of membrane-bound ligands with receptors expressed on target cells to stimulate downstream intracellular pathways. EV-based therapeutics may be directly used as substitutes of intact cells or after modification for targeted drug delivery. However, for the development of EV-based therapeutics, several production, isolation, and characterization requirements have to be met and the quality of the final product has to be tested before its clinical implementation. In this review, we discuss the challenges associated with the development of EV-based therapeutics and the regulatory specifications for their successful clinical translation.

Human Adipose-Derived Stem Cells’ Paracrine Factors in Conditioned Medium Can Enhance Porcine Oocyte Maturation and Subsequent Embryo Development

“…Recent studies suggested that stem cell-derived factors, called “biomaterials”, could improve the development of preimplantation embryos [ 16 , 17 ]. The secreted factors derived from the stem cells in the medium are referred to as extracellular vesicles [ 18 ]. Therefore, the medium is named the conditioned medium (CM) [ 19 ].…”

Extracellular vesicles derived from fibroblasts promote wound healing by optimizing fibroblast and endothelial cellular functions

“…Despite intense research of EVs in wound healing, only mesenchymal stem cell‐derived EVs (MSC‐EVs) have been studied and shown to make a positive contribution to wound healing 27‐32 . EVs isolation from MSCs has some of drawbacks: culture and expansion of MSCs, which could take several days or weeks; red blood cell contamination during isolation; limited cell viability and neovascularization capacity, and isolation of MSCs from bone marrow is highly invasive 33‐35 . So, identifying other potential cell‐derived pro‐wound healing EVs is urgently required for feasible utilization of EV therapy to accelerate wound healing.…”

Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration

“…Because different protocols for purification of EVs may lead to different results, including the purity and yield, it is critical to define the standard isolation of EVs as described above and it needs to be recognized that it is likely that each MSC-EV preparation leads to a different product. The challenges related to the clinical translation of MSC-EVs have also extensively been discussed in a recent article (Maumus et al, 2020 ).…”