A collagen-glycosaminoglycan scaffold supports adult rat mesenchymal stem cell differentiation along osteogenic and chondrogenic routes.
Adult mesenchymal stem cells have the proclivity to differentiate along multiple lineages giving rise to new bone, cartilage, muscle, or fat. Collagen, a normal constituent of bone, provides strength and structural stability and is therefore a potential candidate for use as a substrate on which to engineer bone and cartilage from their respective mesenchymal-derived precursors. In this study, a collagen- glycosaminoglycan scaffold was used to provide a suitable three-dimensional (3-D) environment on which to culture adult rat mesenchymal stem cells and induce differentiation along the osteogenic and chondrogenic lineages. The results demonstrate that adult rat mesenchymal stem cells can undergo osteogenesis when grown on the collagen-glycosaminoglycan scaffold and stimulated with osteogenic factors (dexamethasone, ascorbic acid, beta-glycerophosphate), as evaluated by the temporal induction of the bone-specific proteins, collagen I and osteocalcin, and subsequent matrix mineralization. The osteogenic factors were coupled to activation of the extracellular-regulated protein kinase (ERK), and this kinase was found to play a role in the osteogenic process. As well as supporting osteogenesis, when the cell-seeded scaffold was exposed to chondrogenic factors (dexamethasone and TGF-1beta), collagen II immunoreactivity was increased, providing evidence that the scaffold can also provide a suitable 3-D environment that supports chondrogenesis.
Farrell
Eric
E
Trinity Centre for Bioengineering, Trinity College, Dublin, Ireland., Department of Physiology, Trinity College, Dublin, Ireland.
O'Brien
Fergal J
FJ
Doyle
Paul
P
Fischer
Jan
J
Yannas
Ionnais
I
Harley
Brendan A
BA
O'Connell
Brian
B
Prendergast
Patrick J
PJ
Campbell
Veronica A
VA
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001672:Biocompatible Materials; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology; D003094:Collagen; D024042:Collagen Type I / Q000096:biosynthesis; D024043:Collagen Type II / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D005994:Glycerophosphates / Q000494:pharmacology; D006025:Glycosaminoglycans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008903:Minerals / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D001672:Biocompatible Materials; D024042:Collagen Type I; D024043:Collagen Type II; D005994:Glycerophosphates; D006025:Glycosaminoglycans; D008903:Minerals; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; D003907:Dexamethasone; D003094:Collagen; D020929:Mitogen-Activated Protein Kinase Kinases; D001205:Ascorbic Acid; C031463:beta-glycerophosphoric acid