Consistent osteoblastic differentiation of human mesenchymal stem cells with bone morphogenetic protein 4 and low serum.
Providing fully mature and functional osteoblasts is challenging for bone tissue engineering and regenerative medicine. Such cells could be obtained from multipotent bone marrow mesenchymal stem cells (MSCs) after induction by different osteogenic factors. However, there are some discrepancies in results, notably due to the use of sera and to the type of osteogenic factor. In this study, we compared the osteogenic differentiation of bone marrow MSCs induced by dexamethasone (Dex) or bone morphogenetic proteins (BMPs) by assessing phenotypes in vitro and functional osteoblasts in vivo. Reducing the content of fetal calf serum from 10% to 2% significantly increased the mineral deposition and expression of osteoblastic markers during osteogenesis. In comparison to Dex condition, the addition of BMP4 greatly improved the differentiation of MSCs into fully mature osteoblasts as seen by high expression of Osterix. These results were confirmed in different supportive matrixes, plastic flasks, or biphasic calcium phosphate biomaterials. In contrast to Dex-derived osteoblasts, BMP4-derived osteoblasts from MSCs were significantly able to produce new bone in subcutis of nude mice in accordance with in vitro results. In conclusion, we describe a convenient ex vivo method to produce consistently mature functional osteoblasts from human MSCs with use of BMP4 and low serum.
Cordonnier
Thomas
T
Laboratory for Bone Resorption Physiopathology and Primary Bone Tumors Therapy, Faculty of Medicine, INSERM U957, Nantes, France.
Langonné
Alain
A
Sohier
Jérôme
J
Layrolle
Pierre
P
Rosset
Philippe
P
Sensébé
Luc
L
Deschaseaux
Frédéric
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002516:Ceramics / Q000494:pharmacology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics; D044967:Serum / Q000378:metabolism*; D054457:Tissue Scaffolds / Q000737:chemistry
D055415:Bone Morphogenetic Protein 4; D000469:Alkaline Phosphatase