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Generation of induced pluripotent stem cells from human kidney mesangial cells

Song, Bi and Niclis, Jonathan C and Alikhan, Maliha A and Sakkal, Samy and Sylvain, Aude and Kerr, Peter G and Laslett, Andrew L and Bernard, Claude A and Ricardo, Sharon D (2011) Generation of induced pluripotent stem cells from human kidney mesangial cells. Journal of the American Society of Nephrology, 22 (7). pp. 1213-1220. ISSN 1046-6673

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Abstract

Glomerular injury and podocyte loss leads to secondary tubulointerstitial damage and the development of fibrosis. The possibility of genetically reprogramming adult cells, termed induced pluripotent stem cells (iPS), may pave the way for patient-specific stem-cell-based therapies. Here, we reprogrammed normal human mesangial cells to pluripotency by retroviral transduction using defined factors (OCT4, SOX2, KLF4 and c-Myc). The kidney iPS (kiPS) cells resembled human embryonic stem-cell-like colonies in morphology and gene expression: They were alkaline phosphatase-positive; expressed OCT3/4, TRA-1 to 60 and TRA-1 to 81 proteins; and showed downregulation of mesangial cell markers. Quantitative (qPCR) showed that kiPS cells expressed genes analogous to embryonic stem cells and exhibited silencing of the retroviral transgenes by the fourth passage of differentiation. Furthermore, kiPS cells formed embryoid bodies and expressed markers of all three germ layers. The injection of undifferentiated kiPS colonies into immunodeficient mice formed teratomas, thereby demonstrating pluripotency. These results suggest that reprogrammed kidney induced pluripotent stem cells may aid the study of genetic kidney diseases and lead to the development of novel therapies.

Item Type: Article
Uncontrolled Keywords: ResPubID25076, chronic kidney disease, renal failure, glomerular disorders, podocyte loss, renal regeneration, induced pluripotent stem cells, iPS cells, normal human mesangial cells, NHMCs
Subjects: FOR Classification > 1004 Medical Biotechnology
FOR Classification > 1199 Other Medical and Health Sciences
SEO Classification > 970111 Expanding Knowledge in the Medical and Health Sciences
Faculty/School/Research Centre/Department > Institute of Sport, Exercise and Active Living (ISEAL)
Depositing User: VUIR
Date Deposited: 18 Dec 2012 05:31
Last Modified: 15 Jan 2015 00:57
URI: http://vuir.vu.edu.au/id/eprint/10391
DOI: 10.1681/ASN.2010101022
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Citations in Scopus: 23 - View on Scopus

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