LAUSR

Owing to the low immunogenicity and high target affinities, mesenchymal stem/stromal cell-derived extracellular vesicles (MSC-EVs) have been considered promising therapeutics for disease treatments. However, MSC-EVs that are harvested from different tissues present unique biological features reflective of their origins. The heterogeneity of MSC-EVs constitutes an important barrier to their precise application in clinical translation that may probably lead to uncertain therapeutic effects. To give hints for future clinical translation, we employed five MSCs, whose derived EVs were most intensively utilized, namely bone marrow mesenchymal stem/stromal cells (BMMSCs), umbilical cord stem/stromal cells (UCSCs), adipose-derived stem/stromal cells (ASCs), dermal stem/stromal cells (DSCs) and dental pulp stem/stromal cells (DPSCs) and documented the heterogeneity landscape of the corresponding MSC-EVs. Overall, the basic parameters, stability, and biosafety of different MSC-EVs are indiscriminate. Strikingly, UCSC-EVs exhibited distinguishing productivity. UCSC-EVs as well as DPSC-EVs presented better drug loading/delivery capacity, providing novel insights into their future translational application as promising candidates. In addition, the heterogeneity of different MSC-EVs in cargo diversity, cellular affinity, organ biodistribution, and therapeutic effects may cue the rational selection in different disease treatments. Through a combined assessment, we may provide a rational strategy for selecting MSC-EVs in future clinics. Offering a panoramic view of MSC-EVs harvested from different tissues, our current study may provide guidelines for the precise selection of MSC-EVs in next-generation therapeutics. This article is protected by copyright. All rights reserved.