TREATMENT

VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) FOR CELL-BASED GENE THERAPY OF OSTEONECROSIS

Kornelis A. Poelstra MD PhD, Joshua X Li MD, Quanjun Cui MD, Gary Balian PhD and Gwo-Jaw Wang MD.
Orthopaedic Research Laboratory, University of Virginia, Box 800374, Cobb Hall, Charlottesville, VA 22908. Ph: (804) 924-5181 kap7c@virginia.edu

Introduction: Vascular Endothelial Growth Factor (VEGP) is a potent mitogen for endothelial cells, responsible for the generation of new blood vessels in e.g., endochondral ossification. VEGF, usually generated under hypoxic conditions, apparently does not become available, or, if produced at all, does not stimulate surrounding cells in osteonecrosis.

Methods: Mixed human mesenchymal stromal cells were harvested (Percoll® centrifugation) from a femoral head, and infected with an in-house generated adenoviral construct with mouse VEGF (Ad-mVEGF).

Results: ELISA quantification over 10 days exhibited a 17,500 fold increase in VEGF production in-vitro (mVEGF: from 54pg/10⁶cells to 0.96g/10⁶cells, human VEGF consistently at -60pg/10⁶cells)

Discussion: Intra-operative, ex-situ infection with VEGF and re-implantation of the cells should be investigated as a potential therapeutic measure against osteonecrosis. The Ad-mVEGF construct designed, build, and used in this study, allowed for significant increases in VEGF production, while cell-based gene delivery ensures the presence of a potentially responsive matrix for neo-angiogenesis.