title: Mesenchymal stem cell chondrogenesis: composite growth factor-bioreactor synergism for human stem cell chondrogenesis.
abstract: BACKGROUND
  Effective mesenchymal stem cell chondrogenesis can be accomplished by using a tailored mechanical-biochemical stimulus. To achieve this requires parallel suppression of hypertrophy and osteogenesis.
  
  
  METHODS
  We compared the effects of isolated bioreactor stimulation, isolated growth factor (TGF-β1 or IGF-1) application and their combined stimulation on human bone marrow-derived mesenchymal stem cells cultured within 3D scaffolds. Free-swelling cell-matrix constructs underwent identical growth factor stimulation for control.
  
  
  RESULTS
  Mechanical stimulation provoked stronger chondrogenic differentiation than free-swelling culture. Chondrogenesis by the addition of TGF-β1 was enhanced compared with single physical stimulation. There were no such effects under the influence of IGF-1 alone. Composite application of multiaxial mechanical stimulation plus TGF-β1 and IGF-1 not only triggered the strongest chondrogenesis overall, but also the strongest hypertrophy and osteogenesis.
  
  
  CONCLUSIONS
  Bioreactor-induced chondrogenic differentiation of human mesenchymal stem cells can be effectively enhanced by growth factor addition, while the partially effective suppression of unwanted signs of endochondral ossification requires further scientific input.
authors.affiliation: Department of Orthopaedic & Trauma Surgery, University Medical Center, Albert-Ludwigs University Freiburg, Hugstetter Straße 49, 79095 Freiburg, Germany.
authors.forename: Marios
authors.initials: M
authors.lastname: Petrou
authors.forename: Philipp
authors.initials: P
authors.lastname: Niemeyer
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stoddart
authors.forename: Sibylle
authors.initials: S
authors.lastname: Grad
authors.forename: Anke
authors.initials: A
authors.lastname: Bernstein
authors.forename: Hermann O
authors.initials: HO
authors.lastname: Mayr
authors.forename: Gerrit
authors.initials: G
authors.lastname: Bode
authors.forename: Norbert
authors.initials: N
authors.lastname: Sudkamp
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.forename: Gian M
authors.initials: GM
authors.lastname: Salzmann
mesh_terms: D019149:Bioreactors; D054337:Cell Dedifferentiation / Q000187:drug effects / Q000235:genetics; D020219:Chondrogenesis / Q000187:drug effects* / Q000235:genetics; D004247:DNA / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D006025:Glycosaminoglycans; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D004247:DNA