Vascular Endothelial Growth Factor Sequestration Enhances In Vivo Cartilage Formation

• Published in: International journal of molecular sciences 2017-11, Vol.18 (11), p.2478
• Main Authors: Medeiros Da Cunha, Carolina M, Perugini, Valeria, Bernegger, Petra, Centola, Matteo, Barbero, Andrea, Guildford, Anna L, Santin, Matteo, Banfi, Andrea, Martin, Ivan, Marsano, Anna
• Format: Article
• Language: English
• Subjects: Angiogenesis; Antiangiogenics; Autografts; Cartilage; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; Chondrogenesis; Chondrogenesis - drug effects; Collagen; collagen scaffold; dendron; Differentiation; Human Umbilical Vein Endothelial Cells; Humans; Hyaline Cartilage - drug effects; Hyaline Cartilage - metabolism; Implantation; nasal chondrocyte; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Ossification; Peptide Fragments - pharmacology; Peptides; Scaffolds; soluble VEGF receptor-2; Surgical implants; Transplantation; Transplants & implants; Vascular endothelial growth factor; Vascular endothelial growth factor receptor 2; Vascular Endothelial Growth Factor Receptor-2 - chemistry; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Vascular Endothelial Growth Factors - antagonists & inhibitors; Vascular Endothelial Growth Factors - metabolism; Vascular Endothelial Growth Factors - pharmacology
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18112478

Autologous chondrocyte transplantation for cartilage repair still has unsatisfactory clinical outcomes because of inter-donor variability and poor cartilage quality formation. Re-differentiation of monolayer-expanded human chondrocytes is not easy in the absence of potent morphogens. The Vascular Endothelial Growth Factor (VEGF) plays a master role in angiogenesis and in negatively regulating cartilage growth by stimulating vascular invasion and ossification. Therefore, we hypothesized that its sole microenvironmental blockade by either VEGF sequestration by soluble VEGF receptor-2 (Flk-1) or by antiangiogenic hyperbranched peptides could improve chondrogenesis of expanded human nasal chondrocytes (NC) freshly seeded on collagen scaffolds. Chondrogenesis of several NC donors was assessed either in vitro or ectopically in nude mice. VEGF blockade appeared not to affect NC in vitro differentiation, whereas it efficiently inhibited blood vessel ingrowth in vivo. After 8 weeks, in vivo glycosaminoglycan deposition was approximately two-fold higher when antiangiogenic approaches were used, as compared to the control group. Our data indicates that the inhibition of VEGF signaling, independently of the specific implementation mode, has profound effects on in vivo NC chondrogenesis, even in the absence of chondroinductive signals during prior culture or at the implantation site.