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Article first published online: 19 DEC 2012
Copyright © 2012 AlphaMed Press
Volume 31, Issue 1, pages 117–125, January 2013
How to Cite
Zhu, X.-Y., Urbieta-Caceres, V., Krier, J. D., Textor, S. C., Lerman, A. and Lerman, L. O. (2013), Mesenchymal Stem Cells and Endothelial Progenitor Cells Decrease Renal Injury in Experimental Swine Renal Artery Stenosis Through Different Mechanisms. STEM CELLS, 31: 117–125. doi: 10.1002/stem.1263
Author contributions: X-Y.Z.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; V.U-C and J.D.K.: collection and/or assembly of data and final approval of manuscript; S. C. T. and A.L.: data interpretation, manuscript review, and final approval of manuscript; L.O.L.: conception and design, financial support, administrative support, data interpretation, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS October 23, 2012.
- Issue published online: 19 DEC 2012
- Article first published online: 19 DEC 2012
- Accepted manuscript online: 23 OCT 2012 06:43AM EST
- Manuscript Accepted: 23 SEP 2012
- Manuscript Revised: 7 SEP 2012
- Manuscript Received: 16 MAY 2012
- NIH. Grant Numbers: DK73608, DK77013, HL77131, HL085307
- Progenitor cells;
- Renal artery stenosis;
- Oxidative stress;
- Endoplasmic reticulum stress
Endothelial progenitor cells (EPC) and mesenchymal stem cells (MSC) augment tissue repair but possess slightly different properties. How the cellular phenotype affects the efficacy of this approach in renovascular disease is incompletely understood. This study tested the hypothesis that EPC and MSC protect the poststenotic kidney by blunting different disease pathways. Peripheral blood EPC and adipose-derived MSC were expanded and characterized by cell surface markers (e.g., CD34/kinase insert domain receptor, or CD44/CD90). Single-kidney hemodynamics and function were assessed in pigs after 10 weeks of renal artery stenosis (RAS) treated 4 weeks earlier with an intrarenal infusion of vehicle (n = 7), EPC (RAS+EPC) or MSC (RAS+MSC) (both 10 × 106, n = 6), and normal controls (n = 7). Kidney disease mechanisms were evaluated ex vivo. The ability of EPC and MSC to attenuate endoplasmic reticulum (ER) stress was also studied in isolated ER and in tubular cells cocultured with EPC and MSC. Glomerular filtration rate in RAS was lower than controls, increased in RAS+EPC, and further improved in RAS+MSC, although both improved renal blood flow similarly. EPC prominently enhanced renal growth factor expression and decreased oxidative stress, while MSC more significantly attenuated renal inflammation, ER stress, and apoptosis. Furthermore, MSC induced a greater decrease in caspase-3 and CHOP expression in cultured tubular cells through mechanisms involving cell contact. EPC and MSC achieve a comparable decrease of kidney injury in RAS by different mechanisms, although MSC elicited slightly superior improvement of renal function. These results support development of cell-based approaches for management of renovascular disease and suggest cell selection based on the underlying pathophysiology of kidney injury. STEM Cells2013;31:117–125