title: Generation of induced pluripotent stem cells from human kidney mesangial cells.
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.
authors.affiliation: Monash Immunology and Stem Cell Laboratories (MISCL), Monash University, Building 75, West Ring Road, Clayton Victoria 3800, Australia.
authors.forename: Bi
authors.initials: B
authors.lastname: Song
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Niclis
authors.forename: Maliha A
authors.initials: MA
authors.lastname: Alikhan
authors.forename: Samy
authors.initials: S
authors.lastname: Sakkal
authors.forename: Aude
authors.initials: A
authors.lastname: Sylvain
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kerr
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Laslett
authors.forename: Claude A
authors.initials: CA
authors.lastname: Bernard
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Ricardo
mesh_terms: D000293:Adolescent; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D007668:Kidney / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D050527:Mesangial Cells / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489427:MYC protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors