title: Effects of in vitro low oxygen tension preconditioning of adipose stromal cells on their in vivo chondrogenic potential: application in cartilage tissue repair.
abstract: OBJECTIVE
  Multipotent stromal cell (MSC)-based regenerative strategy has shown promise for the repair of cartilage, an avascular tissue in which cells experience hypoxia. Hypoxia is known to promote the early chondrogenic differentiation of MSC. The aim of our study was therefore to determine whether low oxygen tension could be used to enhance the regenerative potential of MSC for cartilage repair.
  
  
  METHODS
  MSC from rabbit or human adipose stromal cells (ASC) were preconditioned in vitro in control or chondrogenic (ITS and TGF-β) medium and in 21 or 5% O2. Chondrogenic commitment was monitored by measuring COL2A1 and ACAN expression (real-time PCR). Preconditioned rabbit and human ASC were then incorporated into an Si-HPMC hydrogel and injected (i) into rabbit articular cartilage defects for 18 weeks or (ii) subcutaneously into nude mice for five weeks. The newly formed tissue was qualitatively and quantitatively evaluated by cartilage-specific immunohistological staining and scoring. The phenotype of ASC cultured in a monolayer or within Si-HPMC in control or chondrogenic medium and in 21 or 5% O2 was finally evaluated using real-time PCR.
  
  
  CONCLUSIONS
  5% O2 increased the in vitro expression of chondrogenic markers in ASC cultured in induction medium. Cells implanted within Si-HPMC hydrogel and preconditioned in chondrogenic medium formed a cartilaginous tissue, regardless of the level of oxygen. In addition, the 3D in vitro culture of ASC within Si-HPMC hydrogel was found to reinforce the pro-chondrogenic effects of the induction medium and 5% O2. These data together indicate that although 5% O2 enhances the in vitro chondrogenic differentiation of ASC, it does not enhance their in vivo chondrogenesis. These results also highlight the in vivo chondrogenic potential of ASC and their potential value in cartilage repair.
authors: INSERM, Institut National de la Santé et de la Recherche Médicale, Unit 791, Center for Osteoarticular and Dental Tissue Engineering, Group STEP Skeletal Tissue Engineering and Physiopathology, Nantes, France.
authors: Sophie
authors: S
authors: Portron
authors: Christophe
authors: C
authors: Merceron
authors: Olivier
authors: O
authors: Gauthier
authors: Julie
authors: J
authors: Lesoeur
authors: Sophie
authors: S
authors: Sourice
authors: Martial
authors: M
authors: Masson
authors: Borhane Hakim
authors: BH
authors: Fellah
authors: Olivier
authors: O
authors: Geffroy
authors: Elodie
authors: E
authors: Lallemand
authors: Pierre
authors: P
authors: Weiss
authors: Jérôme
authors: J
authors: Guicheux
authors: Claire
authors: C
authors: Vinatier
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002356:Cartilage / Q000293:injuries* / Q000502:physiology / Q000601:surgery*; D018929:Cell Culture Techniques / Q000379:methods; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010100:Oxygen / Q000378:metabolism*; D011817:Rabbits; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*
chemical_list: D010100:Oxygen
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