Combinatorial Analysis of Growth Factors Reveals the Contribution of Bone Morphogenetic Proteins to Chondrogenic Differentiation of Human Periosteal Cells.
Mendes, Luis Filipe; Tam, Wai Long; Chai, Yoke Chinet al.
2016 • In Tissue Engineering. Part C, Methods, 22 (5), p. 473-86
[en] 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 experiment (DoE) strategy to screen the effect of multiple GFs (BMP2, BMP6, GDF5, TGF-beta1, and FGF2) on chondrogenic differentiation of human periosteum-derived mesenchymal stem cells (hPDCs) in vitro. In a micromass culture (muMass) system, BMP2 had a positive effect on glycosaminoglycan deposition at day 7 (p < 0.001), which in combination with BMP6 synergistically enhanced cartilage-like tissue formation that displayed in vitro mineralization capacity at day 14 (p < 0.001). Gene expression of muMasses cultured for 7 days with a medium formulation supplemented with 100 ng/mL of BMP2 and BMP6 and a low concentration of GDF5, TGF-beta1, and FGF2 showed increased expression of Sox9 (1.7-fold) and the matrix molecules aggrecan (7-fold increase) and COL2A1 (40-fold increase) compared to nonstimulated control muMasses. 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 muMasses 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 medium formulations for skeletal tissue engineering approaches.
Disciplines :
Engineering, computing & technology: Multidisciplinary, general & others
Author, co-author :
Mendes, Luis Filipe
Tam, Wai Long
Chai, Yoke Chin
Geris, Liesbet ; Université de Liège > Département d'aérospatiale et mécanique > Génie biomécanique
Luyten, Frank P.
Roberts, Scott J.
Language :
English
Title :
Combinatorial Analysis of Growth Factors Reveals the Contribution of Bone Morphogenetic Proteins to Chondrogenic Differentiation of Human Periosteal Cells.
Publication date :
2016
Journal title :
Tissue Engineering. Part C, Methods
ISSN :
1937-3384
eISSN :
1937-3392
Publisher :
Mary Ann Liebert, United States
Volume :
22
Issue :
5
Pages :
473-86
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
FP7 - 279100 - BRIDGE - Biomimetic process design for tissue regeneration: from bench to bedside via in silico modelling
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