title: Effects of GSK3 inhibitors on in vitro expansion and differentiation of human adipose-derived stem cells into adipocytes.
abstract: BACKGROUND
  Multipotent stem cells exist within adipose tissue throughout life. An abnormal recruitment of these adipose precursor cells could participate to hyperplasia of adipose tissue observed in severe obesity or to hypoplasia of adipose tissue observed in lipodystrophy. Therefore, pharmacological molecules that control the pool of stem cells in adipose tissue are of great interest. Glycogen Synthase Kinase (GSK) 3 has been previously described as involved in differentiation of preadipose cells and might be a potential therapeutic target to modulate proliferation and differentiation of adipocyte precursors. However, the impact of GSK3 inhibition on human adipose-derived stem cells remained to be investigated. The aim of this study was to investigate GSK3 as a possible target for pharmacological inhibition of stem cell adipogenesis. To reach this goal, we studied the effects of pharmacological inhibitors of GSK3, i.e. lithium chloride (LiCl) and BIO on proliferation and adipocyte differentiation of multipotent stem cells derived from human adipose tissue.
  
  
  RESULTS
  Our results showed that GSK3 inhibitors inhibited proliferation and clonogenicity of human stem cells, strongly suggesting that GSK3 inhibitors could be potent regulators of the pool of adipocyte precursors in adipose tissue. The impact of GSK3 inhibition on differentiation of hMADS cells was also investigated. Adipogenic and osteogenic differentiations were inhibited upon hMADS treatment with BIO. Whereas a chronic treatment was required to inhibit osteogenesis, a treatment that was strictly restricted to the early step of differentiation was sufficient to inhibit adipogenesis.
  
  
  CONCLUSIONS
  These results demonstrated the feasibility of a pharmacological approach to regulate adipose-derived stem cell function and that GSK3 could represent a potential target for controlling adipocyte precursor pool under conditions where fat tissue formation is impaired.
authors.affiliation: Institute of Signalling, Biology of Development and Cancer, University of Nice Sophia- Antipolis, CNRS 6543, 28 avenue Valrose, 06100 Nice, France. zaragosi@unice.fr
authors.forename: Laure-Emmanuelle
authors.initials: LE
authors.lastname: Zaragosi
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wdziekonski
authors.forename: Coralie
authors.initials: C
authors.lastname: Fontaine
authors.forename: Phi
authors.initials: P
authors.lastname: Villageois
authors.forename: Pascal
authors.initials: P
authors.lastname: Peraldi
authors.forename: Christian
authors.initials: C
authors.lastname: Dani
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride