Promise(s) of Mesenchymal Stem Cells as an In Vitro Model System to Depict Pre-DiabeticDiabetic Milieu in WNINGR-Ob Mutant Rats 英文参考文献.docVIP

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Promise(s) of Mesenchymal Stem Cells as an In Vitro Model System to Depict Pre-DiabeticDiabetic Milieu in WNINGR-Ob Mutant Rats 英文参考文献.doc

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Promise(s) of Mesenchymal Stem Cells as an In Vitro Model System to Depict Pre-DiabeticDiabetic Milieu in WNINGR-Ob Mutant Rats 英文参考文献

Promise(s)ofMesenchymalStemCellsasanInVitro ModelSystemtoDepictPre-Diabetic/DiabeticMilieuin WNIN/GR-ObMutantRats SoundaryaL.Madhira1,SatyaS.Challa1,ManiprabhaChalasani1,GiridharanNappanveethl2, RameshR.Bhonde3,RajannaAjumeera1,VijayalakshmiVenkatesan1* 1DepartmentofBiochemistry/StemCellResearch,NationalInstituteofNutrition,Hyderabad,AndhraPradesh,India,2NationalCentreforLaboratoryAnimalSciences, NationalInstituteofNutrition,Hyderabad,AndhraPradesh,India,3ManipalInstituteofRegenerativeMedicine,Bangalore,Karnataka,India Abstract Background: Development of model systems have helped to a large extent, in bridging gap to understand the mechanism(s) of disease including diabetes. Interestingly, WNIN/GR-Ob rats (Mutants),established at National Centre for LaboratoryAnimals(NCLAS)ofNationalInstituteofNutrition(NIN),formasuitablemodelsystemtostudyobesitywithType 2 diabetes (T2D) demonstrating several secondary complications (cataract, cardiovascular complications, infertility, nephropathy etc).The presentstudyhasbeencarried outtoexplore thepotent application(s) ofmultipotentstemcells suchasbonemarrowmesenchymalstemcells(BM-MSCs),toportrayfeaturesofpre-diabetic/T2Dvis-a`-visfeaturingobesity, withimpairedglucosetolerance(IGT),hyperinsulinemia(HI)andinsulinresistance(IR)seenwithMutantratsakintohuman situation. Methodology/PrincipalFindings:PrimaryculturesofBM-MSCs(thirdpassage)fromMutants,itsleanlittermate(Lean)and parentalcontrol(Control)werecharacterizedfor:proliferationmarkers,diseasememorytomarkobesity/T2D/HI/IRwhich included phased gene expression studies for adipogenic/pancreatic lineages, inflammatory markers and differentiation ability to form mature adipocytes/Insulin-like cellular aggregates (ILCAs). The data showed that BM-MSCs from Mutant demonstrated a state of disease memory, depicted by an upregulated expression of inflammatory markers (IL-6, TNFa); increasedstemcellrecruitment(Oct-4,Sox-2)andproliferationrates(CD90+/CD29+,PDA,‘S’phaseofcellcyclebyFACSand