High efficient adenoviral-mediated VEGF and Ang-1 gene delivery into osteogenically differentiated human mesenchymal stem cells.
Survival of ex vivo constructed tissues after transplantation is limited by insufficient oxygen and nutrient supply. Therefore, strategies aiming at improvement of neovascularization of engineered tissues are a key issue in tissue engineering applications. This in vitro study aimed at exploring the usability of osteogenically differentiated human mesenchymal stem cells (MSCs) as carriers of the angiogenic growth factor genes vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) for therapeutic angiogenesis in bone tissue engineering. The ex vivo adenoviral vector mediated transduction into osteogenically differentiated MSCs revealed a highly efficient and long lasting expression of the transgenes. Biological activity of VEGF and Ang-1 secreted from transduced cells was confirmed by analyzing the sprouting, proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) in response to conditioned medium obtained from transduced cells. The transduced osteogenically differentiated MSCs described in this report may be suitable for inducing neovascularization in bone tissue engineering applications.
Klöpper
Jonas
J
Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Freiburg, Germany.
Lindenmaier
Werner
W
Fiedler
Ulrike
U
Mehlhorn
Alexander
A
Stark
G Björn
GB
Finkenzeller
Günter
G
D000256:Adenoviridae / Q000235:genetics*; D053687:Adult Stem Cells / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis; D018874:Spheroids, Cellular; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A