Department of Surgery, University Hospital Basel, and Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
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.
Int J Mol Sci. 2017 Nov 21;18(11):2478. 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.
自体软骨细胞移植用于软骨修复仍然存在不理想的临床效果，因为存在供体间的变异性和软骨质量形成不良。在缺乏有效形态发生素的情况下，单层扩增的人软骨细胞不容易重新分化。血管内皮生长因子（VEGF）在血管生成中起主要作用，并通过刺激血管浸润和骨化来负调控软骨生长。因此，我们假设通过可溶性血管内皮生长因子受体-2（Flk-1）或抗血管生成的超支肽来单独阻断其微环境，可以改善新鲜接种在胶原支架上的扩增人鼻软骨细胞（NC）的软骨生成。我们评估了多个 NC 供体的体外或裸鼠异位软骨生成情况。VEGF 阻断似乎不会影响 NC 的体外分化，但在体内能有效抑制血管内生长。8 周后，与对照组相比，使用抗血管生成方法后体内糖胺聚糖沉积增加约两倍。我们的数据表明，VEGF 信号的抑制，无论采用何种特定的实施方式，都会对体内 NC 软骨生成产生深远影响，即使在培养前或植入部位没有软骨诱导信号的情况下也是如此。
