Inhibition of blood vessel formation by a chondrocyte-derived extracellular matrix.

Abstract

In this study, the chondrocyte-derived extracellular matrix (CECM) was evaluated

for its activity to inhibit vessel invasion in vitro and in vivo. Human umbilical

vein endothelial cells (HUVECs) and rabbit chondrocytes were plated on a

bio-membrane made of CECM or human amniotic membrane (HAM). The adhesion,

proliferation, and tube formation activity of HUVECs and chondrocytes were

examined. The CECM and HAM powders were then mixed individually in Matrigel and

injected subcutaneously into nude mice to examine vessel invasion in vivo after 1

week. Finally, a rabbit model of corneal neovascularization (NV) was induced by

3-point sutures in the upper cornea, and CECM and HAM membranes were implanted

onto the corneal surface at day 5 after suture injury. The rabbits were

sacrificed at 7 days after transplantation and the histopathological analysis was

performed. The adhesion and proliferation of HUVECs were more efficient on the

HAM than on the CECM membrane. However, chondrocytes on each membrane showed an

opposite result being more efficient on the CECM membrane. The vessel invasion in

vivo also occurred more deeply and intensively in Matrigel containing HAM than in

the one containing CECM. In the rabbit NV model, CECM efficiently inhibited the

neovessels formation and histological remodeling in the injured cornea. In

summary, our findings suggest that CECM, an integral cartilage ECM composite,

shows an inhibitory effect on vessel invasion both in vitro and in vivo, and

could be a useful tool in a variety of biological and therapeutic applications

including the prevention of neovascularization after cornea injury.