Journal
SCIENCE ADVANCES
Volume 6, Issue 33, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaz0748
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Funding
- National Natural Science Foundation of China [81720108007, 81670696, 81470922, 31671194]
- National Key Research and Development Program [2018YFC1314000]
- Clinic Research Center of Jiangsu Province [BL2014080]
- Major State Basic Research Development Program of China [2012CB517706]
- Postgraduate Research and Practice Innovation Program of Jiangsu Province [KYCX18_0171]
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Recently, extracellular vesicles (EVs) have been attracting strong research interest for use as natural drug delivery systems. We report an approach to manufacturing interleukin-10 (IL-10)-loaded EVs (IL-10(+) EVs) by engineering macrophages for treating ischemic acute kidney injury (AKI). Delivery of IL-10 via EVs enhanced not only the stability of IL-10, but also its targeting to the kidney due to the adhesive components on the EV surface. Treatment with IL-10(+) EVs significantly ameliorated renal tubular injury and inflammation caused by ischemia/reperfusion injury, and potently prevented the transition to chronic kidney disease. Mechanistically, IL-10(+) EVs targeted tubular epithelial cells, and suppressed mammalian target of rapamycin signaling, thereby promoting mitophagy to maintain mitochondrial fitness. Moreover, IL-10(+) EVs efficiently drove M2 macrophage polarization by targeting macrophages in the tubulointerstitium. Our study demonstrates that EVs can serve as a promising delivery platform to manipulate IL-10 for the effective treatment of ischemic AKI.
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