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Int J Mol Sci. 2017 Nov 21;18(11). pii: E2478. doi: 10.3390/ijms18112478.

Vascular Endothelial Growth Factor Sequestration Enhances In Vivo Cartilage Formation.

Author information

1
Department of Surgery, University Hospital Basel, and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland. carol_medeiros@yahoo.com.
2
Brighton Studies in Tissue-mimicry and Aided Regeneration, Centre for Regenerative Medicine and Devices, University of Brighton, Huxley Building Lewes Road, Brighton BN2 4GJ, UK. v.perugini@brighton.ac.uk.
3
Department of Surgery, University Hospital Basel, and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland. petrabernegger@gmail.com.
4
Department of Surgery, University Hospital Basel, and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland. mcentola@anikatherapeutics.com.
5
Department of Surgery, University Hospital Basel, and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland. andrea.barbero@usb.ch.
6
Brighton Studies in Tissue-mimicry and Aided Regeneration, Centre for Regenerative Medicine and Devices, University of Brighton, Huxley Building Lewes Road, Brighton BN2 4GJ, UK. anna@etaliauk.com.
7
Brighton Studies in Tissue-mimicry and Aided Regeneration, Centre for Regenerative Medicine and Devices, University of Brighton, Huxley Building Lewes Road, Brighton BN2 4GJ, UK. M.Santin@brighton.ac.uk.
8
Department of Surgery, University Hospital Basel, and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland. andrea.banfi@usb.ch.
9
Department of Surgery, University Hospital Basel, and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland. Ivan.martin@usb.ch.
10
Department of Surgery, University Hospital Basel, and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland. Anna.Marsano@usb.ch.

Abstract

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.

KEYWORDS:

chondrogenesis; collagen scaffold; dendron; nasal chondrocyte; soluble VEGF receptor-2

PMID:
29160845
PMCID:
PMC5713444
DOI:
10.3390/ijms18112478
[Indexed for MEDLINE]
Free PMC Article

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