Extracellular Vesicles from Induced Mesenchymal Stem Cells Inhibit Acute Kidney Injury to Chronic Kidney Disease Transition.

Abstract

Compared with conventional mesenchymal stem cells (MSCs), induced mesenchymal stem cells (iMSCs) from induced pluripotent stem cells are unique cell sources for tissue regeneration. The effect of extracellular vesicles (EVs) secreted from iMSCs on inhibiting acute kidney injury (AKI) to chronic kidney disease (CKD) transition was not reported. In this study, we investigated whether EVs from iMSCs (iMSC-EVs) could inhibit AKI-to-CKD transition. iMSC-EVs exhibited the general characteristics of EVs, such as protein marker expression, morphology, and size. Additionally, iMSC-EVs were detected in renal tissues after intravenous injection. In human renal tubular epithelial cells, the increase in pro-fibrotic gene expression in response to transforming growth factor β1 treatment was decreased by iMSC-EVs. In a mouse model of the AKI-to-CKD transtion induced by folic acid, repeated administration of iMSC-EVs restored renal function at day 14. Specifically, iMSC-EVs reduced interstitial fibrosis, sustained inflammation, various types of cell death, and the number of immune cells infiltrating kidneys. Capillary rarefaction in renal tissue was also reversed by iMSC-EVs. Our results demonstrate that iMSC-EVs reduced interstitial fibrosis, inflammation, and cell death occurring during the CKD transition after AKI. Thus, iMSC-EVs have the potential to block AKI-to-CKD transition.