Vitronectin modulates human mesenchymal stem cell response to insulin-like growth factor-I and transforming growth factor beta 1 in a serum-free environment.
The use of animal sera for the culture of therapeutically important cells impedes the clinical use of the cells. We sought to characterize the functional response of human mesenchymal stem cells (hMSCs) to specific proteins known to exist in bone tissue with a view to eliminating the requirement of animal sera. Insulin-like growth factor-I (IGF-I), via IGF binding protein-3 or -5 (IGFBP-3 or -5) and transforming growth factor-beta 1 (TGF-beta(1)) are known to associate with the extracellular matrix (ECM) protein vitronectin (VN) and elicit functional responses in a range of cell types in vitro. We found that specific combinations of VN, IGFBP-3 or -5, and IGF-I or TGF-beta(1) could stimulate initial functional responses in hMSCs and that IGF-I or TGF-beta(1) induced hMSC aggregation, but VN concentration modulated this effect. We speculated that the aggregation effect may be due to endogenous protease activity, although we found that neither IGF-I nor TGF-beta(1) affected the functional expression of matrix metalloprotease-2 or -9, two common proteases expressed by hMSCs. In summary, combinations of the ECM and growth factors described herein may form the basis of defined cell culture media supplements, although the effect of endogenous protease expression on the function of such proteins requires investigation.
Parker
Tony
T
Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia. a.parker@qut.edu.au
Upton
Zee
Z
Leavesley
David
D
D000369:Aged, 80 and over; D002449:Cell Aggregation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D019096:Vitronectin / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D053773:Transforming Growth Factor beta1; D019096:Vitronectin; D007334:Insulin-Like Growth Factor I; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9