Open AccessShort‐Term BMP‐2 Expression Is Sufficient for In Vivo Osteochondral Differentiation of Mesenchymal Stem Cells
Author(s) -
Noël Danièle,
Gazit Dan,
Bouquet Celine,
Apparailly Florence,
Bony Claire,
Plence Pascale,
Millet Virginie,
Turgeman Gadi,
Perricaudet Michel,
Sany Jacques,
Jorgensen Christian
Publication year - 2004
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.22-1-74
Subject(s) - mesenchymal stem cell , biology , microbiology and biotechnology , bone morphogenetic protein 2 , cartilage , stem cell , stem cell transplantation for articular cartilage repair , clinical uses of mesenchymal stem cells , bone morphogenetic protein , cellular differentiation , chondrogenesis , bone morphogenetic protein 7 , immunology , adult stem cell , anatomy , in vitro , genetics , gene
Currently available murine models to evaluate mesenchymal stem cell (MSC) differentiation are based on cell injection at ectopic sites such as muscle or skin. Due to the importance of environmental factors on the differentiation capacities of stem cells in vivo, we investigated whether the peculiar synovial/cartilaginous environment may influence the lineage specificity of bone morphogenetic protein (BMP)‐2‐engineered MSCs. To this aim, we used the C3H10T1/2‐derived C9 MSCs that express BMP‐2 under control of the doxycycline (Dox)‐repressible promoter, Tet‐Off, and showed in vitro, using the micropellet culture system that C9 MSCs kept their potential to differentiate toward chondrocytes. Implantation of C9 cells, either into the tibialis anterior muscles or into the joints of CB17‐severe combined immunodeficient bg mice led to the formation of cartilage and bone filled with bone marrow as soon as day 10. However, no differentiation was observed after injection of naïve MSCs or C9 cells that were repressed to secrete BMP‐2 by Dox addition. The BMP‐2‐induced differentiation of adult MSCs is thus independent of soluble factors present in the local environment of the synovial/cartilaginous tissues. Importantly, we demonstrated that a short‐term expression of the BMP‐2 growth factor is necessary and sufficient to irreversibly induce bone formation, suggesting that a stable genetic modification of MSCs is not required for stem cell‐based bone/cartilage engineering.