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Combinatorial analysis of growth factors reveals the contribution of bone morphogenetic proteins to chondrogenic differentiation of human periosteal cells

Journal Contribution - Journal Article

Successful application of cell-based strategies in cartilage and bone tissue engineering has been hampered by the lack of robust protocols to efficiently differentiate mesenchymal stem cells into the chondrogenic lineage. The development of chemically defined culture media supplemented with growth factors (GFs) has been proposed as a way to overcome this limitation. In this work we applied a fractional Design of Experiments (DoE) strategy to screen the effect of multiple GFs (BMP2; BMP6; GDF5; TGF-β1; FGF2) in chondrogenic differentiation of human periosteum-derived mesenchymal stem cells (hPDCs) in vitro. In a micromass culture (µMass) system, BMP2 had a positive effect on Glycosaminoglycan (GAG) deposition at day 7 (p<0.001), which in combination with BMP6 synergistically enhanced cartilage-like tissue formation that displayed in vitro mineralisation capacity at day 14 (p<0.001). Gene expression of µMasses cultured for 7 days with a medium formulation supplemented with 100 ng/mL of BMP2 and BMP6 and low concentration of GDF5, TGF-β1 and FGF2 showed increased expression of Sox9 (1.7 fold), and the matrix molecules aggrecan (7 fold increase) and COL2A1 (40 fold increase) when compared to non-stimulated control µMasses. The DoE analysis indicated that in GF combinations, BMP2 was the strongest effector for chondrogenic differentiation of hPDCs. When transplanted ectopically in nude mice, the in vitro differentiated µMasses showed maintenance of the cartilaginous phenotype after 4 weeks in vivo. This study indicates the power of using the DoE approach for the creation of new media formulations in skeletal tissue engineering approaches.
Journal: Tissue Engineering. Part C. Methods
ISSN: 1937-3384
Issue: 5
Volume: 22
Pages: 473 - 486
Publication year:2016
BOF-keylabel:yes
IOF-keylabel:yes
BOF-publication weight:1
CSS-citation score:1
Authors:International
Authors from:Higher Education
Accessibility:Closed