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Short-term BMP-2 expression is sufficient for in vivo osteochondral differentiation of mesenchymal stem cells.
- Source :
-
Stem cells (Dayton, Ohio) [Stem Cells] 2004; Vol. 22 (1), pp. 74-85. - Publication Year :
- 2004
-
Abstract
- 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.
- Subjects :
- Animals
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins genetics
Bone and Bones cytology
Bone and Bones embryology
Bone and Bones metabolism
Cartilage embryology
Cartilage metabolism
Cell Communication physiology
Cell Differentiation genetics
Cell Lineage genetics
Chondrocytes cytology
Chondrocytes metabolism
Extracellular Fluid metabolism
Gene Expression Regulation, Developmental genetics
Growth Substances metabolism
Joints cytology
Joints growth & development
Joints surgery
Mice
Mice, Inbred C3H
Muscle, Skeletal cytology
Muscle, Skeletal growth & development
Muscle, Skeletal surgery
NIH 3T3 Cells
Osteogenesis genetics
Promoter Regions, Genetic drug effects
Promoter Regions, Genetic genetics
Stem Cell Transplantation
Bone Morphogenetic Proteins biosynthesis
Cartilage cytology
Cell Differentiation physiology
Mesenchymal Stem Cells cytology
Mesenchymal Stem Cells metabolism
Osteogenesis physiology
Transforming Growth Factor beta
Subjects
Details
- Language :
- English
- ISSN :
- 1066-5099
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Stem cells (Dayton, Ohio)
- Publication Type :
- Academic Journal
- Accession number :
- 14688393
- Full Text :
- https://doi.org/10.1634/stemcells.22-1-74