Abstract
Extracellular vesicles (EVs) are cell-derived membrane structures enclosing proteins, lipids, RNAs, metabolites, growth factors, and cytokines. EVs have emerged as essential intercellular communication regulators in multiple physiological and pathological processes. Previous studies revealed that mesenchymal stem cells (MSCs) could either support or suppress tumor progression in different cancers by paracrine signaling via MSC-derived EVs. Evidence suggested that MSC-derived EVs could mimic their parental cells, possessing pro-tumor and anti-tumor effects, and inherent tumor tropism. Therefore, MSC-derived EVs can be a cell-free cancer treatment alternative. This review discusses different insights regarding MSC-derived EVs' roles in cancer treatment and summarizes bioengineered MSC-derived EVs’ applications as safe and versatile anti-tumor agent delivery platforms. Meanwhile, current hurdles of moving MSC-derived EVs from bench to bedside are also discussed.
Highlights
Extracellular vesicles (EVs) are nano-sized bilayerenclosed membrane structures containing proteins, lipids, RNAs, metabolites, growth factors, and cytokines, acting as versatile transporters between cells [1]
EVs for therapeutic applications are typically derived from mesenchymal stem cells (MSCs), a cell type well characterized for EV mass production [6]
UBR2 expression was increased in gastric cancer cells treated with the exosomes, enhancing tumor growth and metastasis via the Wnt/β-catenin pathway. These results suggested that exosomal miRNAs, lncRNAs, mRNAs, and proteins can be transported into target cells and play specific roles
Summary
Extracellular vesicles (EVs) are nano-sized bilayerenclosed membrane structures containing proteins, lipids, RNAs, metabolites, growth factors, and cytokines, acting as versatile transporters between cells [1]. The more common application of EVs is based on their transport properties in delivering functional cargoes to targeted cells, rendering them attractive as drug delivery vehicles. EVs for therapeutic applications are typically derived from mesenchymal stem cells (MSCs), a cell type well characterized for EV mass production [6]. By increasing centrifugation speed and/or time in a stepwise manner, it can separate particles with different sedimentation rates, remove undesired components during each centrifugation This approach cannot distinguish particles with overlapping ranges, such as exosomes and microvesicles. Size exclusion chromatography, and filtration present similar problems, depending on particle density or size for separation Different from these physical-based isolation methods, affinity capture can separate EVs with high-purity but with low-yield via EV surface markers interaction with the capture molecules attached to different carriers (e.g., magnetic beads) [29]. Positive protein markers should include at least one transmembrane/lipid-bound
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