title: Promise(s) of mesenchymal stem cells as an in vitro model system to depict pre-diabetic/diabetic milieu in WNIN/GR-Ob mutant rats.
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 Laboratory Animals (NCLAS) of National Institute of Nutrition (NIN), form a suitable model system to study obesity with Type 2 diabetes (T2D) demonstrating several secondary complications (cataract, cardiovascular complications, infertility, nephropathy etc). The present study has been carried out to explore the potent application(s) of multipotent stem cells such as bone marrow mesenchymal stem cells (BM-MSCs), to portray features of pre-diabetic/T2D vis-à-vis featuring obesity, with impaired glucose tolerance (IGT), hyperinsulinemia (HI) and insulin resistance (IR) seen with Mutant rats akin to human situation.
  
  
  RESULTS
  Primary cultures of BM-MSCs (third passage) from Mutants, its lean littermate (Lean) and parental control (Control) were characterized for: proliferation markers, disease memory to mark obesity/T2D/HI/IR which 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, TNFα); increased stem cell recruitment (Oct-4, Sox-2) and proliferation rates (CD90+/CD29+, PDA, 'S' phase of cell cycle by FACS and BrdU incorporation); accelerated preadipocyte induction (Dact-1, PPARγ2) with a quantitative increase in mature adipocyte formation (Leptin); ILCAs, which were non-responsive to high glucose did confer the Obese/T2D memory in Mutants. Further, these observations were in compliance with the anthropometric data.
  
  
  CONCLUSIONS
  Given the ease of accessibility and availability of MSCs, the present study form the basis to report for the first time, application of BM-MSCs as a feasible in vitro model system to portray the disease memory of pre-clinical/T2D with IR - a major metabolic disorder of global concern.
authors.affiliation: Department of Biochemistry/Stem Cell Research, National Institute of Nutrition, Hyderabad, Andhra Pradesh, India.
authors.forename: Soundarya L
authors.initials: SL
authors.lastname: Madhira
authors.forename: Satya S
authors.initials: SS
authors.lastname: Challa
authors.forename: Maniprabha
authors.initials: M
authors.lastname: Chalasani
authors.forename: Giridharan
authors.initials: G
authors.lastname: Nappanveethl
authors.forename: Ramesh R
authors.initials: RR
authors.lastname: Bhonde
authors.forename: Rajanna
authors.initials: R
authors.lastname: Ajumeera
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Venkatesan
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D039902:Multipotent Stem Cells / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011236:Prediabetic State / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors; D014409:Tumor Necrosis Factor-alpha