Induced pluripotent stem cells as a model for diabetes investigation

• DOI: 10.1038/srep08597
• Publication Date: 2015-02-26T10:14:13Z
• Authors: J. Stepniewski; N. Kachamakova-Tr...; D. Ogrocki; M. Szopa; M. Matlok; M. Beilharz; G. Dyduch; M. T. Malecki; A. Jozkowicz; J. Dulak
• Keywords: Adult; Homeodomain Proteins; Male; 0301 basic medicine; Induced Pluripotent Stem Cells; Lewis X Antigen; Mice, Obese; Nuclear Proteins; Cell Differentiation; Nanog Homeobox Protein; Middle Aged; Article; 3. Good health; Mice, Inbred C57BL; 03 medical and health sciences; Diabetes Mellitus, Type 2; Animals; Humans; Female; Octamer Transcription Factor-3; Biomarkers; Cells, Cultured; Embryoid Bodies; Endothelial Progenitor Cells

AbstractMouse and human induced pluripotent stem cells (iPSCs) may represent a novel approach for modeling diabetes. Taking this into consideration, the aim of this study was to generate and evaluate differentiation potential of iPSCs from lepdb/db (db/db) mice, the model of diabetes type 2 as well as from patients with Maturity Onset Diabetes of the Young 3 (HNF1A MODY). Murine iPSC colonies from both wild type and db/db mice were positive for markers of pluripotency: Oct3/4A, Nanog, SSEA1, CDy1 and alkaline phosphatase and differentiated in vitro and in vivo into cells originating from three germ layers. However, our results suggest impaired differentiation of db/db cells into endothelial progenitor-like cells expressing CD34 and Tie2 markers and their reduced angiogenic potential. Human control and HNF1A MODY reprogrammed cells also expressed pluripotency markers: OCT3/4A, SSEA4, TRA-1–60, TRA-1-81, formed embryoid bodies (EBs) and differentiated into cells of three germ layers. Additionally, insulin expressing cells were obtained from those partially reprogrammed cells with direct as well as EB-mediated differentiation method. Our findings indicate that disease-specific iPSCs may help to better understand the mechanisms responsible for defective insulin production or vascular dysfunction upon differentiation toward cell types affected by diabetes.