Inhibition of blood vessel formation by a chondrocyte-derived extracellular matrix.
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.
Department of Advanced Biomedical Sciences, College of Medicine, Inha University, Incheon, Republic of Korea.
Byung Hyune
BH
Choi
Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea; Cell Therapy Center, Ajou Medical Center, Suwon, Republic of Korea.
Kyoung-Hwan
KH
Choi
Ocular Neovascular Disease Research Center, Inje University Busan Paik Hospital, Busan, Republic of Korea.
Hye Sook
HS
Lee
Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea; Cell Therapy Center, Ajou Medical Center, Suwon, Republic of Korea.
Bo Ram
BR
Song
Department of Physiology, College of Medicine, Inha University, Incheon, Republic of Korea.
So Ra
SR
Park
Ocular Neovascular Disease Research Center, Inje University Busan Paik Hospital, Busan, Republic of Korea; Department of Ophthalmology, Inje University College of Medicine, Busan Paik Hospital, Busan, Republic of Korea. Electronic address: oculoplasty@gmail.com.
Jae Wook
JW
Yang
Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea; Cell Therapy Center, Ajou Medical Center, Suwon, Republic of Korea; Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon, Republic of Korea. Electronic address: bhmin@ajou.ac.kr.
Byoung-Hyun
BH
Min
D000726:Androgen Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000737:chemistry* / Q000166:cytology; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011817:Rabbits; D054457:Tissue Scaffolds / Q000737:chemistry
D000726:Androgen Antagonists; D001672:Biocompatible Materials
Anti-angiogenesis; Biomaterial; Chondrocyte-derived extracellular matrix; Corneal neovascularization; Vessel invasion