http://jasn.asnjournals.org/content/early/2011/05/19/ASN.2010101022.abstract?sid=5d0a6b7a-92f3-4d29-8f18-352c144e521cBi Song*, Jonathan C. Niclis*, Maliha A. Alikhan*, Samy Sakkal*, Aude Sylvain*, Peter G. Kerr†, Andrew L. Laslett‡§, Claude A. Bernard* and Sharon D. Ricardo*
+ Author Affiliations
*Monash Immunology and Stem Cell Laboratories, Monash University;
†Department of Medicine, Monash Medical Centre, Australia, Clayton, Australia;
‡CSIRO Materials Science and Engineering, Clayton, Australia;
§Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia
Correspondence:
Sharon D. Ricardo, Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Building 75, West Ring Road, Clayton Victoria 3800, Australia. Phone: +613 9905 0671; Fax: +613 9905 0680 E-mail: Sharon.Ricardo@monash.edu.
Received for publication October 3, 2010.
Accepted for publication February 22, 2011.
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.
Copyright © 2011 by the American Society of Nephrology