title: Cartilage Oligomeric Matrix Protein Angiopoeitin-1 Provides Benefits During Nerve Regeneration In Vivo and In Vitro.
abstract: Our group pioneered the study of nerve regeneration in China and has successfully developed human "acellular nerve grafts (ACNGs)". However, our clinical studies revealed that the effects of ACNGs for long and large nerve defects are far from satisfactory. To improve the efficacy of ACNGs, we combined Cartilage oligomeric matrix protein angiopoietin-1 (COMP-Ang1) with ACNGs in rat sciatic nerve injury models and observed the outcomes via angiographic, morphological, and functional analyses. Co-cultures of endothelial cells (ECs) and dorsal root ganglion neurons (DRGs) were also used to characterize the relationship between neovascularization and nerve regeneration. The results showed significant improvements in early neovascularization, nerve regeneration, and functional outcomes in vivo in the ACNG + COMP-Ang1 group. In vitro, neurite length, and density as well as the expression levels of neurofilament 68 (NF68) and phosphorylated-Tie-2 (p-Tie-2) significantly increased when ECs were co-cultured with DRGs using COMP-Ang1. p-Tie-2 expression dramatically decreased after treatment with a Tie-2 kinase inhibitor (S157701), which consequently decreased the level of NF68. COMP-Ang1 can be concluded to promote early neovascularization followed by brisk nerve regeneration, and the mechanism of this regeneration may involve the modulation of the p-Tie-2 and Tie-2 receptors on ECs. These findings demonstrate that ACNGs can be modified using COMP-Ang1 to improve their efficacy in repairing peripheral nerve defects in clinical trials.
authors.affiliation: Department of Orthopedics and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Longhai
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Orthopedics and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China. hebodoc@gmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Orthopedics and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China. 56273609@qq.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Orthopedics and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Orthopedics and Microsurgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Jiakai
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D016900:Neurofilament Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D012584:Sciatic Nerve / Q000098:blood supply / Q000293:injuries / Q000502:physiology*; D019737:Transplants
chemical_list: C515576:COMP-Ang1 fusion protein; D016900:Neurofilament Proteins; D011993:Recombinant Fusion Proteins; C066858:neurofilament protein NF 68; D042787:Receptor, TIE-2
keywords: Acellular nerve graft; Extracellular matrix; Neovascularization; Nerve regeneration; Tissue engineering