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

Helmrich, U. and Di Maggio, N. and Guven, S. and Groppa, E. and Melly, L. and Largo, R. D. and Heberer, M. and Martin, I. and Scherberich, A. and Banfi, A.. (2013) Osteogenic graft vascularization and bone resorption by VEGF-expressing human mesenchymal progenitors. Biomaterials, 34 (21). pp. 5025-5035.

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Official URL: http://edoc.unibas.ch/dok/A6243406

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Bewegungsapparat und Integument > Plastische, rekonstruktive, ästhetische und Handchirurgie (Schaefer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Bewegungsapparat und Integument > Plastische, rekonstruktive, ästhetische und Handchirurgie (Schaefer)
03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung > Chirurgische Forschung (Heberer)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Querschnittsbereich Forschung > Chirurgische Forschung (Heberer)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Cell and Gene Therapy (Banfi)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Tissue Engineering (Martin)
03 Faculty of Medicine
UniBasel Contributors:Martin, Ivan and Banfi, Andrea and Heberer, Michael and Scherberich, Arnaud
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:0142-9612
e-ISSN:1878-5905
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Oct 2017 11:42
Deposited On:23 May 2014 08:34

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