title: Induced pluripotent stem cells as a model for diabetes investigation.
abstract: 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.
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Stepniewski
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: N
authors.initials: N
authors.lastname: Kachamakova-Trojanowska
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Ogrocki
authors.affiliation: 1] Clinic of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland [2] University Hospital Krakow Poland.
authors.forename: M
authors.initials: M
authors.lastname: Szopa
authors.affiliation: II Clinic of General Surgery, Collegium Medicum, Jagiellonian University, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Matlok
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Beilharz
authors.affiliation: Department of Clinical and Experimental Pathomorphology, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: G
authors.initials: G
authors.lastname: Dyduch
authors.affiliation: 1] Clinic of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland [2] University Hospital Krakow Poland.
authors.forename: M T
authors.initials: MT
authors.lastname: Malecki
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Jozkowicz
authors.affiliation: 1] Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland [2] Malopolska Centre of Biotechnology, Jagiellonian University, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Dulak
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D058732:Embryoid Bodies / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D016256:Lewis X Antigen / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D009687:Nuclear Proteins / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D016256:Lewis X Antigen; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse