title: Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia.
abstract: This study examines the effect and mechanism of action of Netrin-1 on bone marrow mesenchymal stem cells in angiogenesis. Tube formation and migration of bone marrow mesenchymal stem cells were observed in cell culture. Bone marrow mesenchymal stem cells or Netrin-1-bone marrow mesenchymal stem cells were injected into the ischaemic area of the rat hind limb on the first day after surgery. Laser Doppler perfusion imaging was performed to analyse the levels of vascular endothelial growth factor in plasma and muscles, and immunohistochemistry and immunofluorescence were used to analyse angiogenesis. Bone marrow mesenchymal stem cells in medium containing Netrin-1 markedly increased the number of tubes formed and the migration of bone marrow mesenchymal stem cells compared with the untreated control group. The function of Netrin-1 in tube formation and migration is similar to vascular endothelial growth factor, and combined with vascular endothelial growth factor, Netrin-1 has more enhanced effect than in the other three groups. The Netrin-1-bone marrow mesenchymal stem cell group had better augmented blood-perfusion scores and vessel densities, as well as improved function of the ischaemic limb than that of the group injected with bone marrow mesenchymal stem cells (treated with bone marrow mesenchymal stem cells individually) or the control group (treated with medium). These results suggest that Netrin-1 has the ability to augment the angiogenesis of bone marrow mesenchymal stem cells and improve the function of the ischaemic hind limb by increasing the level of vascular endothelial growth factor.
authors.affiliation: Department of Neurology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
authors.forename: Xianjin
authors.initials: X
authors.lastname: Ke
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Chenxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China shygu@njmu.edu.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007511:Ischemia / Q000628:therapy*; D035002:Lower Extremity / Q000503:physiopathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D000075388:Netrin-1; D017207:Rats, Sprague-Dawley; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; C000617354:Ntn1 protein, rat; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D000075388:Netrin-1
keywords: Netrin-1; angiogenesis; diabetes; mesenchymal stem cell; peripheral vascular disease