Induced pluripotent stem cells as a model for diabetes investigation

Mouse 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 lep db/db (db/db) mice, the model of diabetes type 2 as well as from...

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Bibliographic Details
Published in:	Scientific reports Vol. 5; no. 1; p. 8597
Main Authors:	Stepniewski, J., Kachamakova-Trojanowska, N., Ogrocki, D., Szopa, M., Matlok, M., Beilharz, M., Dyduch, G., Malecki, M. T., Jozkowicz, A., Dulak, J.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 26-02-2015 Nature Publishing Group
Subjects:	13/1 13/100 13/31 13/44 13/51 14/34 38 38/77 38/88 42 631/532/1360 631/532/2064/2158 Adult Alkaline phosphatase Angiogenesis Animals Biomarkers CD34 antigen Cell Differentiation Cells, Cultured Diabetes Diabetes mellitus Diabetes Mellitus, Type 2 - pathology Embryoid Bodies - metabolism Endothelial Progenitor Cells - metabolism Female Homeodomain Proteins - metabolism Humanities and Social Sciences Humans Induced Pluripotent Stem Cells - metabolism Insulin Lewis X Antigen - metabolism Male Mice, Inbred C57BL Mice, Obese Middle Aged multidisciplinary Nanog Homeobox Protein Nuclear Proteins - metabolism Oct-4 protein Octamer Transcription Factor-3 - metabolism Pluripotency Rodents Science Stem cell transplantation Stem cells
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Summary:	Mouse 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 lep db/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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2045-2322 2045-2322
DOI:	10.1038/srep08597