Osteogenic medium is superior to growth factors in differentiation of human adipose stem cells towards bone-forming cells in 3D culture.
Human adipose stem cells (hASCs) have been recently used to treat bone defects in clinical practice. Yet there is a need for more optimal scaffolds and cost-effective approaches to induce osteogenic differentiation of hASCs. Therefore, we compared the efficiency of bone morphogenetic proteins (BMP-2 and BMP-7), vascular endothelial growth factor (VEGF), and osteogenic medium (OM) for the osteo-induction of hASCs in 3D culture. In addition, growth factors were tested in combination with OM. Commercially available bioactive glass scaffolds (BioRestore) and biphasic calcium phosphate granules (BoneCeramic) were evaluated as prospective carriers for hASCs. Both biomaterials supported hASC-viability, but BioRestore resulted in higher cell number than BoneCeramic, whereas BoneCeramic supported more significant collagen production. The most efficient osteo-induction was achieved with plain OM, promoting higher alkaline phosphatase activity and collagen production than growth factors. In fact, treatment with BMP-2 or VEGF did not increase osteogenic differentiation or cell number significantly more than maintenance medium with either biomaterial. Moreover, BMP-7 treatment consistently inhibited proliferation and osteogenic differentiation of hASCs. Interestingly, there was no benefit from growth factors added to OM. This is the first study to demonstrate that OM enhances hASC-differentiation towards bone-forming cells significantly more than growth factors in 3D culture.
Adult Stem Cells, Institute of Biomedical Technology, University of Tampere, Tampere, Finland.
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L
Tirkkonen
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S
Haimi
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Huttunen
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J
Wolff
E
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Pirhonen
G K
GK
Sándor
S
S
Miettinen
D000273:Adipose Tissue / Q000166:cytology; D053687:Adult Stem Cells / Q000502:physiology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology / Q000502:physiology*; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003470:Culture Media; D005898:Glass / Q000737:chemistry; D006801:Humans; D006882:Hydroxyapatites / Q000737:chemistry; D059630:Mesenchymal Stem Cells / Q000502:physiology; D010012:Osteogenesis; D016062:Porosity; D013499:Surface Properties; D046509:Tissue Culture Techniques; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000502:physiology*
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; C558777:BoneCeramic; D003470:Culture Media; D006882:Hydroxyapatites; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D000469:Alkaline Phosphatase