Human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (hucMSC-sEVs) have been demonstrated as a therapeutic agent to prevent and treat cisplatin-induced acute kidney injury (AKI). However, hucMSC-sEVs still face many problems and challenges in the repair and treatment of tissue injury, including short circulation time, insufficient targeting, and low therapeutic efficacy. Therefore, we constructed engineered hybrid vesicles fused with nanovesicles derived from human neutrophil membranes and hucMSC-sEVs, named neutrophil membrane engineered hucMSC-sEVs (NEX). NEX significantly enhanced the targeting of hucMSC-sEVs to injured kidney tissues, improved the impaired renal function via reducing pro-inflammatory cytokines expression, promoted the proliferation of renal tissue cells, and inhibited renal cell apoptosis in vivo. In addition, NEX enhanced hucMSC-sEVs uptake by NRK52E cells, but inhibited its uptake by RAW264.7 cells. Moreover, administration of NEX reduced cellular oxidative stress and promoted proliferation of NRK52E cells treated with cisplatin in vitro. In summary, our findings indicate that this design of a universal approach enhances the targeting and therapeutic efficacy of hucMSC-sEVs in kidney tissue regeneration, and provides new evidence promoting its clinical application.

Aging shows a decline in overall physical function, and cellular senescence is the powerful catalyst leading to aging. Considering that aging will be accompanied with the emergence of various aging-related diseases, research on new antiaging drugs is still valuable. Extracellular vesicles (EVs), as tools for intercellular communication, are important components of the senescence-associated secretory phenotype (SASP), and they can play pathological roles in the process of cellular senescence. In addition, EVs are similar to their original cells in functions. Therefore, EVs derived from pathological tissues or body fluids may be closely related to the progression of diseases and become potential biomarkers, while those from healthy cells may have therapeutic effects. Moreover, EVs are satisfactory drug carriers. At present, numerous studies have supported the idea that engineered EVs could improve drug targeting ability and utilization efficiency. Here, we summarize the characteristics of EVs and cellular senescence and focus on the diagnostic and therapeutic potential of EVs in various aging-related diseases, including Alzheimer disease, osteoporosis, cardiovascular disease, diabetes mellitus and its complications, and skin aging.