Renal scattered tubular-like cells confer protective effects in the stenotic murine kidney mediated by release of extracellular vesicles

• Published in: Scientific reports Vol. 8; no. 1; pp. 1263 - 12
• Main Authors: Zou, Xiangyu, Kwon, Soon Hyo, Jiang, Kai, Ferguson, Christopher M., Puranik, Amrutesh S., Zhu, Xiangyang, Lerman, Lilach O.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19-01-2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/51; 14/34; 59/57; 631/532/2118; 692/4022/1585/104; Animals; Cells, Cultured; Coculture Techniques; Dactinomycin - toxicity; Electron microscopy; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Extracellular vesicles; Extracellular Vesicles - metabolism; Extracellular Vesicles - transplantation; Fibrosis; Hemodynamics; Humanities and Social Sciences; Kidney Tubules - cytology; Kidneys; Male; Membrane potential; Membrane Potential, Mitochondrial; Mice; Mitochondria; multidisciplinary; Oxidation; Oxidative Stress; Oxygenation; Perfusion; Renal artery; Renal Artery Obstruction - therapy; Science; Science (multidisciplinary); Stenosis; Swine
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-19750-y

To test the hypothesis that intrinsic renal scattered tubular cells (STC-like cells) contribute to repairing injured tubular epithelial cells (TEC) by releasing extracellular vesicle (EV). EV released from primary cultured pig STC-like cells were confirmed by electron microscopy. Antimycin-A (AMA)-induced injured proximal TEC (PK1 cells) were co-cultured with STC-like cells, STC-like cells-derived EV, or EV-free conditioned-medium for 3 days. Cellular injury, oxidative stress and mitochondrial function were assessed. Transfer of mitochondria from STC-like cells to TEC was assessed using Mito-trackers, and their viability by mitochondrial membrane potential assays. STC-like cells-derived EV were intra-arterially injected into mice 2 weeks after induction of unilateral renal artery stenosis. Two weeks later, renal hemodynamics were studied using magnetic-resonance-imaging, and renal fibrosis assessed
ex-vivo
. Cultured STC-like cells released EV that were uptaken by TEC. A protective effect conferred by STC-like cells in AMA-induced TEC injury was partly mimicked by their EV. Furthermore, STC-like cells-EV carried and transferred mitochondrial material to injured TEC, which partly restored mitochondrial function.
In vivo
, STC-like cells-derived EV engrafted in the stenotic kidney, and improved its perfusion and oxygenation. STC-like cells-EV exert protective effects on injured tubular cells
in vitro
and
in vivo
, partly by transferring STC-like cells mitochondria, which remain at least partly functional in recipient TEC.