Journal article
Mesenchymal stem cells deliver exogenous MicroRNA-let7c via exosomes to attenuate renal fibrosis
B Wang, K Yao, BM Huuskes, HH Shen, J Zhuang, C Godson, EP Brennan, JL Wilkinson-Berka, AF Wise, SD Ricardo
Molecular Therapy | CELL PRESS | Published : 2016
DOI: 10.1038/mt.2016.90
Abstract
The advancement of microRNA (miRNA) therapies has been hampered by difficulties in delivering miRNA to the injured kidney in a robust and sustainable manner. Using bioluminescence imaging in mice with unilateral ureteral obstruction (UUO), we report that mesenchymal stem cells (MSCs), engineered to overexpress miRNA-let7c (miR-let7c-MSCs), selectively homed to damaged kidneys and upregulated miR-let7c gene expression, compared with nontargeting control (NTC)-MSCs. miR-let7c-MSC therapy attenuated kidney injury and significantly downregulated collagen IV 1, metalloproteinase-9, transforming growth factor (TGF)-β1, and TGF-β type 1 receptor (TGF-βR1) in UUO kidneys, compared with controls. In ..
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Awarded by Science Foundation Ireland
Funding Acknowledgements
B.W. and B.M.H. acknowledge funding support from Monash University and Kidney Health Australia. J.L.W.-B. is a Senior Research Fellow of the National Health and Medical Research Council of Australia. Work in C.G.'s lab is supported by Science Foundation Ireland Awards 06/IN/.1/B114 and 08/US/B1517. The authors acknowledge technical assistance from Alex Fulcher and Keith Schulze (Monash Micro Imaging, Monash University). The 3'UTR of the human TGF-beta R1 was provided by C.G.