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Osteogenic graft vascularization and bone resorption by VEGF-expressing human mesenchymal progenitors.
Journal article

Osteogenic graft vascularization and bone resorption by VEGF-expressing human mesenchymal progenitors.

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  • 2013-04-10
Published in:
  • Biomaterials. - 2013
Acid Phosphatase
Animals
Bone Marrow Cells
Bone Matrix
Bone Resorption
Cathepsin K
Cell Proliferation
Cell Survival
Humans
Isoenzymes
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells
Neovascularization, Physiologic
Osteoclasts
Osteogenesis
Rats
Tartrate-Resistant Acid Phosphatase
Vascular Endothelial Growth Factor A
English Rapid vascularisation of tissue-engineered osteogenic grafts is a major obstacle in the development of regenerative medicine approaches for bone repair. Vascular endothelial growth factor (VEGF) is the master regulator of vascular growth. We investigated a cell-based gene therapy approach to generate osteogenic grafts with an increased vascularization potential in an ectopic nude rat model in vivo, by genetically modifying human bone marrow-derived stromal/stem cells (BMSC) to express rat VEGF. BMSC were loaded onto silicate-substituted apatite granules, which are a clinically established osteo-conductive material. Eight weeks after implantation, the vascular density of constructs seeded with VEGF-BMSC was 3-fold greater than with control cells, consisting of physiologically structured vascular networks with both conductance vessels and capillaries. However, VEGF specifically caused a global reduction in bone quantity, which consisted of thin trabeculae of immature matrix. VEGF did not impair BMSC engraftment in vivo, but strongly increased the recruitment of TRAP- and Cathepsin K-positive osteoclasts. These data suggest that VEGF over-expression is effective to improve the vascularization of osteogenic grafts, but also has the potential to disrupt bone homoeostasis towards excessive degradation, posing a challenge to its clinical application in bone tissue engineering.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/149860
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