Transplantation of MSCs in Combination with Netrin-1 Improves Neoangiogenesis in a Rat Model of Hind Limb Ischemia

Li, Qian; Yao, Dan; Ma, Jianhua; Zhu, Jian; Xu, Xianghong; Ren, Yunli; Xin-sheng, Ding; Mao, Xiao‐Ming

doi:10.1016/j.jss.2009.08.031

Cited by 35 publications

(21 citation statements)

References 24 publications

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“…In a recent report, transplantation of MSCs with recombinant netrin-1 augmented blood vessel density and angiogenic score in a rat model of hind limb ischemia [3]. Concomitant administration of netrin-1 with MSC transplantation regulated VEGF expression in MSCs, which remained significantly elevated for 28 days of observation in the netrin-1/MSC treated animals as compared with the controls.…”

Section: Fig 5 (A)mentioning

confidence: 88%

“…Recent studies have proposed their participation in embryonic and pathological angiogenesis [2,3]. Three secreted netrins (netrins-1, 3 and 4) have been identified in mammals, in addition to the two GPI anchored membranes proteins: netrin-G1 and netrin-G2.…”

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confidence: 99%

“…Netrin-1 is also a potent vascular mitogen and promotes proliferation, migration, and adhesion of endothelial cells and vascular smooth muscle cells [4]. The specific activity of netrin-1 on endothelial cells is comparable to vascular endothelial growth factor and plateletderived growth factor (PDGF); and, therefore, netrin-1 is one of the most extensively studied members of the netrin family of proteins [3,5]. Secreted netrins function via interaction with the six specific receptors to mediate their physiological and pathological effects.…”

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confidence: 99%

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Cytoprotective and Proangiogenic Activity of Ex-Vivo Netrin-1 Transgene Overexpression Protects the Heart Against Ischemia/Reperfusion Injury

Durrani

Haider

Ahmed

et al. 2012

Stem Cells and Development

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In continuation of a previous work that transgene expression of sonic hedgehog promoted neo-vascularization via netrin-1 release, the current study was aimed at assessing the anti-apoptotic and pro-angiogenic role of netrin-1 transgene overexpression in the ischemic myocardium. pLP-Adeno-X ViralTrak vectors containing netrin-1 cDNA amplified from rat mesenchymal stem cells (Ad-netrin) or without a therapeutic gene (Ad-null) were constructed and transfected into HEK-293 cells to produce Ad-netrin and Ad-null vectors. Sca-1 + -like cells were isolated and propagated in vitro and were successfully transduced with Ad-netrin transduced Sca-1 + cells ( Net Sca-1 + ) and Ad-null transduced Sca-1 + cells ( Null Sca-1 + ). Overexpression of netrin-1 in Net Sca-1 + was confirmed by reverse transcription-polymerase chain reaction and western blot. Neonatal cardiomyocytes and rat endothelial cells expressed netrin-1 specific receptor Uncoordinated-5b and the conditioned medium from Net Sca-1 + cells was protective for both the cell types against oxidant stress. For in vivo studies, the rat model of myocardial ischemia/reperfusion injury was developed in female Wistar rats by left anterior descending coronary artery occlusion for 45 min followed by reperfusion. The animals were grouped to receive 70 mL of Dulbecco's modified Eagle's medium without cells (group-1), containing 2 · 10 6 Null Sca-1 + cells (group-2) and Net Sca-1 + cells (group-3). Net Sca-1 + cells significantly reduced ischemia/reperfusion injury in the heart and preserved the global heart function in group-3 (P < 0.05 vs. groups-1 and group-2). Ex-vivo netrin-1 overexpression in the heart increased NOS activity in the heart. Blood vessel density was significantly higher in group-3 (P < 0.05 vs. controls). We concluded that netrin-1 decreased apoptosis in cardiomyocytes and endothelial cells via activation of Akt. Netrin-1 transgene expression was proangiogenic and effectively reduced ischemia/reperfusion injury to preserve global heart function.

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Section: Fig 5 (A)mentioning

confidence: 88%

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confidence: 99%

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confidence: 99%

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Cytoprotective and Proangiogenic Activity of Ex-Vivo Netrin-1 Transgene Overexpression Protects the Heart Against Ischemia/Reperfusion Injury

Durrani

Haider

Ahmed

et al. 2012

Stem Cells and Development

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“…We reported that: 1) a DC EF guided migration of hiPS cells in 2D culture; colonies showed significantly greater directionality than [16,17]; 3) removing the extracellular matrix (ECM) barrier by matrix metalloprotease stimulation to accelerate the migration of stem cells [18]. In addition to those biochemical methods, a biophysical approach using a magnetic field has been shown to offer a guidance cue for the migration of neural stem cells [19].…”

Section: Discussionmentioning

confidence: 99%

Electrically guiding migration of human induced pluripotent stem cells

Zhang¹,

Calafiore²,

Zeng³

et al. 2010

Cell. Biol. Int.

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A major road-block in stem cell therapy is the poor homing and integration of transplanted stem cells with the targeted host tissue. Human induced pluripotent stem (hiPS) cells are considered an excellent alternative to embryonic stem (ES) cells and we tested the feasibility of using small, physiological electric fields (EFs) to guide hiPS cells to their target. Applied EFs stimulated and guided migration of cultured hiPS cells toward the anode, with a stimulation threshold of <30 mV/mm; in three-dimensional (3D) culture hiPS cells remained stationary, whereas in an applied EF they migrated directionally. This is of significance as the therapeutic use of hiPS cells occurs in a 3D environment. EF exposure did not alter expression of the pluripotency markers SSEA-4 and Oct-4 in hiPS cells. We compared EF-directed migration (galvanotaxis) of hiPS cells and hES cells and found that hiPS cells showed greater sensitivity and directedness than those of hES cells in an EF, while hES cells migrated toward cathode. Rho-kinase (ROCK) inhibition, a method to aid expansion and survival of stem cells, significantly increased the motility, but reduced directionality of iPS cells in an EF by 70-80%. Thus, our study has revealed that physiological EF is an effective guidance cue for the migration of hiPS cells in either 2D or 3D environments and that will occur in a ROCKdependent manner. Our current finding may lead to techniques for applying EFs in vivo to guide migration of transplanted stem cells. Keywords Human induced pluripotent stem (hiPS) cell . Electric field (EF) . Cell migration . Wound healing . GalvanotaxisElectronic supplementary material The online version of this article

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“…We have shown that pretreating BMSCs with a recombinant Netrin-1 protein markedly augmented the blood-perfusion score and vessel density, as well as improved function of the ischaemic limb. 20 On the basis of these findings, we constructed a novel recombinant adenovirus Netrin-1 vector (Ad5-EGFPNetrin-1) and successfully infected BMSCs that can express Netrin-1. This study tested the effects of Netrin-1 on the implantation of BMSCs in angiogenesis using the model of hind-limb ischaemia and examined the possible functional mechanism.…”

Section: Introductionmentioning

confidence: 99%

Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia

Liu

Wang

et al. 2016

Diabetes and Vascular Disease Research

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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.

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Transplantation of MSCs in Combination with Netrin-1 Improves Neoangiogenesis in a Rat Model of Hind Limb Ischemia

Cited by 35 publications

References 24 publications

Cytoprotective and Proangiogenic Activity of Ex-Vivo Netrin-1 Transgene Overexpression Protects the Heart Against Ischemia/Reperfusion Injury

Cytoprotective and Proangiogenic Activity of Ex-Vivo Netrin-1 Transgene Overexpression Protects the Heart Against Ischemia/Reperfusion Injury

Electrically guiding migration of human induced pluripotent stem cells

Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia

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