The Experts below are selected from a list of 1578 Experts worldwide ranked by ideXlab platform
François A. Auger - One of the best experts on this subject based on the ideXlab platform.
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Biaxial biomechanical properties of self-assembly tissue-Engineered Blood Vessels
Journal of the Royal Society Interface, 2010Co-Authors: Michael T. Zaucha, Lucie Germain, François A. Auger, Robert Gauvin, Rudolph L. GleasonAbstract:Along with insights into the potential for graft success, knowledge of biomechanical properties of small diameter tissue-Engineered Blood Vessel (TEBV) will enable designers to tailor the Vessels’ mechanical response to closer resemble that of native tissue. Composed of two layers that closely mimic the native media and adventitia, a tissue-Engineered vascular adventitia (TEVA) is wrapped around a tissue-Engineered vascular media (TEVM) to produce a self-assembled tissue-Engineered media/adventia (TEVMA). The current study was undertaken to characterize the biaxial biomechanical properties of TEVM, TEVA and TEVMA under physiological pressures as well as characterize the stress-free reference configuration. It was shown that the TEVA had the greatest compliance over the physiological loading range while the TEVM had the lowest compliance. As expected, compliance of the SATEBV fell in between with an average compliance of 2.73 MPa 21 . Data were used to identify material parameters for a microstructurally motivated constitutive model. Identified material parameters for the TEVA and TEVM provided a good fit to experimental data with an average coefficient of determination of 0.918 and 0.868, respectively. These material parameters were used to develop a two-layer predictive model for the response of a TEVMA which fit well with experimental data.
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a novel single step self assembly approach for the fabrication of tissue Engineered vascular constructs
Tissue Engineering Part A, 2010Co-Authors: Robert Gauvin, François A. Auger, Robert M. Nerem, Taby Ahsan, Danielle Larouche, Philippe Levesque, Jean Dube, Lucie GermainAbstract:There is a clinical need for a functional tissue-Engineered Blood Vessel because small-caliber arterial graft (<5 mm) applications are limited by the availability of suitable autologous Vessels and suboptimal performances of synthetic grafts. This study presents an analysis of the mechanical properties of tissue-Engineered vascular constructs produced using a novel single-step self-assembly approach. Briefly, the tissue-Engineered vascular media were produced by culturing smooth muscle cell in the presence of sodium l-ascorbate until the formation of a cohesive tissue sheet. This sheet was then rolled around a tubular support to create a media construct. Alternatively, the tissue-Engineered vascular adventitia was produced by rolling a tissue sheet obtained from dermal fibroblasts or saphenous vein fibroblasts. The standard self-assembly approach to obtain the two-layer tissue-Engineered vascular constructs comprising both media and adventitia constructs consists of two steps in which tissue-Engineered va...
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applications of human tissue Engineered Blood Vessel models to study the effects of shed membrane microparticles from t lymphocytes on vascular function
Tissue Engineering Part A, 2009Co-Authors: Maria Pricci, François A. Auger, Ramaroson Andriantsitohaina, Jeanmichel Bourget, Hubert Robitaille, Chiara Porro, Raffaella Soleti, Ahmed H Mostefai, Carmen M Martinez, Lucie GermainAbstract:Microparticles (MPs) are membrane vesicles harboring cell surface proteins and containing cytoplasmic components of the original cell. High levels of circulating MPs have been detected in pathological states associated with vascular dysfunction. We took advantage of the self-assembly method of tissue engineering to produce in vitro three vascular constructs from human vascular smooth muscle cells and fibroblasts to investigate the role of the adventitia in the modulation of vascular tone by MPs, comparing the contractile response of each of these constructs to histamine. The first two were composed of an adventitia (tissue-Engineered vascular adventitia (TEVA)) or a media (tissue-Engineered vascular media (TEVM)) solely, and the third one contained a media and an adventitia (tissue-Engineered vascular media and adventitia (TEVMA)). In the three constructs, the results show that histamine induces contraction insensitive to blockade of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2)...
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mechanisms by which e selectin regulates diapedesis of colon cancer cells under flow conditions
Cancer Research, 2008Co-Authors: Pierre-luc Tremblay, Jacques Huot, François A. AugerAbstract:Diapedesis, the passage of circulating tumor cells across the endothelium, is a critical determinant in most cases of metastasis. Using a laminar flow chamber and a tissue-Engineered Blood Vessel, we found that E-selectin is required not only for the initial adhesion and rolling of circulating HT-29 colon cancer cells on the endothelium but also for their subsequent diapedesis. These processes require both the intracellular and extracellular domains of E-selectin. We also identified three distinct mechanisms by which circulating cancer cells interact with E-selectin to initiate their diapedesis: formation of a mosaic between cancer cells and endothelial cells, paracellular diapedesis at the junction of three endothelial cells, and transcellular diapedesis. We also obtained evidence indicating that E-selectin–dependent paracellular extravasation is independent of intercellular adhesion molecule and vascular cell adhesion molecule and that it requires the activation of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase downstream of E-selectin. This is supported by the observation that the adenoviral-mediated expression of the E-selectin mutant Y603F is associated with both an inhibition of ERK and paracellular extravasation. Our study is the first to clearly establish, under dynamic and shear stress conditions, how E-selectin regulates diapedesis of circulating cancer cells. These results provide new insights in understanding the metastatic process. [Cancer Res 2008;68(13):5167–76]
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Adventitia contribution in vascular tone: insights from adventitia-derived cells in a tissue-Engineered human Blood Vessel
The FASEB Journal, 2006Co-Authors: Karina Laflamme, Charles J. Roberge, Murielle Rémy-zolghadri, Stéphanie Pouliot, Raymond Labbé, Pedro D'orléans-juste, Kathleen Baker, Guillaume Grenier, François A. Auger, Lucie GermainAbstract:Whether the adventitia component of Blood Vessels directly participates in the regulation of vascular tone remains to be demonstrated. We have recently developed a human tissue-Engineered Blood Vessel comprising the three tunicae of a native Blood Vessel using the self-assembly approach. To investigate the role of the adventitia in the modulation of vascular tone, this tissue-engineering method was used to produce three vascular constructs from cells explanted and proliferated from donor Vessel tunicae 1) an adventitia + a media, or only 2) an adventitia, or 3) a media. The vasoconstriction responses of these 3 constructs to endothelin, the most potent vasopressor known up-to-date, as well as to nonselective and selective agonists and antagonists, were compared. The adventitia contracted to endothelin-1, -2, whereas the media and the media+adventitia contracted to all three endothelins. Endothelin-induced contraction of the adventitia was dependent on ETA receptors, whereas that of the media and the adven...
Lucie Germain - One of the best experts on this subject based on the ideXlab platform.
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Biaxial biomechanical properties of self-assembly tissue-Engineered Blood Vessels
Journal of the Royal Society Interface, 2010Co-Authors: Michael T. Zaucha, Lucie Germain, François A. Auger, Robert Gauvin, Rudolph L. GleasonAbstract:Along with insights into the potential for graft success, knowledge of biomechanical properties of small diameter tissue-Engineered Blood Vessel (TEBV) will enable designers to tailor the Vessels’ mechanical response to closer resemble that of native tissue. Composed of two layers that closely mimic the native media and adventitia, a tissue-Engineered vascular adventitia (TEVA) is wrapped around a tissue-Engineered vascular media (TEVM) to produce a self-assembled tissue-Engineered media/adventia (TEVMA). The current study was undertaken to characterize the biaxial biomechanical properties of TEVM, TEVA and TEVMA under physiological pressures as well as characterize the stress-free reference configuration. It was shown that the TEVA had the greatest compliance over the physiological loading range while the TEVM had the lowest compliance. As expected, compliance of the SATEBV fell in between with an average compliance of 2.73 MPa 21 . Data were used to identify material parameters for a microstructurally motivated constitutive model. Identified material parameters for the TEVA and TEVM provided a good fit to experimental data with an average coefficient of determination of 0.918 and 0.868, respectively. These material parameters were used to develop a two-layer predictive model for the response of a TEVMA which fit well with experimental data.
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a novel single step self assembly approach for the fabrication of tissue Engineered vascular constructs
Tissue Engineering Part A, 2010Co-Authors: Robert Gauvin, François A. Auger, Robert M. Nerem, Taby Ahsan, Danielle Larouche, Philippe Levesque, Jean Dube, Lucie GermainAbstract:There is a clinical need for a functional tissue-Engineered Blood Vessel because small-caliber arterial graft (<5 mm) applications are limited by the availability of suitable autologous Vessels and suboptimal performances of synthetic grafts. This study presents an analysis of the mechanical properties of tissue-Engineered vascular constructs produced using a novel single-step self-assembly approach. Briefly, the tissue-Engineered vascular media were produced by culturing smooth muscle cell in the presence of sodium l-ascorbate until the formation of a cohesive tissue sheet. This sheet was then rolled around a tubular support to create a media construct. Alternatively, the tissue-Engineered vascular adventitia was produced by rolling a tissue sheet obtained from dermal fibroblasts or saphenous vein fibroblasts. The standard self-assembly approach to obtain the two-layer tissue-Engineered vascular constructs comprising both media and adventitia constructs consists of two steps in which tissue-Engineered va...
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applications of human tissue Engineered Blood Vessel models to study the effects of shed membrane microparticles from t lymphocytes on vascular function
Tissue Engineering Part A, 2009Co-Authors: Maria Pricci, François A. Auger, Ramaroson Andriantsitohaina, Jeanmichel Bourget, Hubert Robitaille, Chiara Porro, Raffaella Soleti, Ahmed H Mostefai, Carmen M Martinez, Lucie GermainAbstract:Microparticles (MPs) are membrane vesicles harboring cell surface proteins and containing cytoplasmic components of the original cell. High levels of circulating MPs have been detected in pathological states associated with vascular dysfunction. We took advantage of the self-assembly method of tissue engineering to produce in vitro three vascular constructs from human vascular smooth muscle cells and fibroblasts to investigate the role of the adventitia in the modulation of vascular tone by MPs, comparing the contractile response of each of these constructs to histamine. The first two were composed of an adventitia (tissue-Engineered vascular adventitia (TEVA)) or a media (tissue-Engineered vascular media (TEVM)) solely, and the third one contained a media and an adventitia (tissue-Engineered vascular media and adventitia (TEVMA)). In the three constructs, the results show that histamine induces contraction insensitive to blockade of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2)...
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Adventitia contribution in vascular tone: insights from adventitia-derived cells in a tissue-Engineered human Blood Vessel
The FASEB Journal, 2006Co-Authors: Karina Laflamme, Charles J. Roberge, Murielle Rémy-zolghadri, Stéphanie Pouliot, Raymond Labbé, Pedro D'orléans-juste, Kathleen Baker, Guillaume Grenier, François A. Auger, Lucie GermainAbstract:Whether the adventitia component of Blood Vessels directly participates in the regulation of vascular tone remains to be demonstrated. We have recently developed a human tissue-Engineered Blood Vessel comprising the three tunicae of a native Blood Vessel using the self-assembly approach. To investigate the role of the adventitia in the modulation of vascular tone, this tissue-engineering method was used to produce three vascular constructs from cells explanted and proliferated from donor Vessel tunicae 1) an adventitia + a media, or only 2) an adventitia, or 3) a media. The vasoconstriction responses of these 3 constructs to endothelin, the most potent vasopressor known up-to-date, as well as to nonselective and selective agonists and antagonists, were compared. The adventitia contracted to endothelin-1, -2, whereas the media and the media+adventitia contracted to all three endothelins. Endothelin-induced contraction of the adventitia was dependent on ETA receptors, whereas that of the media and the adven...
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endothelium properties of a tissue Engineered Blood Vessel for small diameter vascular reconstruction
Journal of Vascular Surgery, 2004Co-Authors: Murielle Remyzolghadri, Lucie Germain, Joanie Laganiere, Jeanfrancois Oligny, François A. AugerAbstract:Abstract Purpose A tissue-Engineered Blood Vessel (TEBV) produced in vitro by the self-assembly method was developed in our laboratory for the replacement of small-diameter Blood Vessels. The interior of this Vessel is covered by an endothelium. The aim of the present study was to evaluate whether the endothelial layer would make a favorable contribution at the time of implantation of the TEBV by investigating in vitro the hemocompatible properties of the endothelial cells covering its interior. Methods The secretion of the von Willebrand factor (vWF) and expression of thrombomodulin by the endothelium were assessed, and the adhesive molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1) were quantified as a function of maturation time. To evaluate the functional response of the endothelium on injury, the cellular response to physiological stimulatory factors (thrombin and lipopolysaccharide [LPS]) was analyzed. Results The endothelial cells formed a confluent monolayer displaying favorable hemocompatible properties (78% ± 10% of cells expressing thrombomodulin with only 12 ± 3 mU/10 6 cells of vWF secreted over a 2-hour period), which acquired their full expression after a culture period of 4 days. Moreover, pro-adhesive properties toward inflammatory cells were not observed. The cells were also able to respond to physiological-stimulating agents (thrombin and LPS) and demonstrated a statistically significant overexpression of the corresponding molecules under the conditions tested. Conclusions These results indicate that the endothelium of the tissue-Engineered Blood Vessel produced by the self-assembly approach displays advantageous qualities with regard to the Vessel's future implantation as a small-diameter vascular prosthesis.
George A. Truskey - One of the best experts on this subject based on the ideXlab platform.
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iPSC-Derived Endothelial Cells Affect Vascular Function in a Tissue-Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome.
Stem cell reports, 2020Co-Authors: Leigh Atchison, Kan Cao, Nadia O. Abutaleb, Elizabeth Snyder-mounts, Yantenew Gete, Alim Ladha, Thomas J. Ribar, George A. TruskeyAbstract:Summary Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder caused by a point mutation in the Lamin A gene that produces the protein progerin. Progerin toxicity leads to accelerated aging and death from cardiovascular disease. To elucidate the effects of progerin on endothelial cells, we prepared tissue-Engineered Blood Vessels (viTEBVs) using induced pluripotent stem cell-derived smooth muscle cells (viSMCs) and endothelial cells (viECs) from HGPS patients. HGPS viECs aligned with flow but exhibited reduced flow-responsive gene expression and altered NOS3 levels. Relative to viTEBVs with healthy cells, HGPS viTEBVs showed reduced function and exhibited markers of cardiovascular disease associated with endothelium. HGPS viTEBVs exhibited a reduction in both vasoconstriction and vasodilation. Preparing viTEBVs with HGPS viECs and healthy viSMCs only reduced vasodilation. Furthermore, HGPS viECs produced VCAM1 and E-selectin protein in TEBVs with healthy or HGPS viSMCs. In summary, the viTEBV model has identified a role of the endothelium in HGPS.
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Real-time observation of leukocyte–endothelium interactions in tissue-Engineered Blood Vessel
Lab on a chip, 2018Co-Authors: Zaozao Chen, Min Tang, D Huang, Weiqian Jiang, Ji Sun Park, Leigh Atchison, George A. TruskeyAbstract:Human cell-based 3D tissue constructs play an increasing role in disease modeling and drug screening. Inflammation, atherosclerosis, and many autoimmune disorders involve the interactions between immune cells and Blood Vessels. However, it has been difficult to image and model these interactions under realistic conditions. In this study, we fabricated a perfusion and imaging chamber to allow the real-time visualization of leukocyte perfusion, adhesion, and migration inside a tissue-Engineered Blood Vessel (TEBV). We monitored the elevated monocyte adhesion to the TEBV wall and transendothelial migration (TEM) as the TEBV endothelium was activated by the inflammatory cytokine TNF-α. We demonstrated that treatment with anti-TNF-α or an NF-kB signaling pathway inhibitor would attenuate the endothelium activation and reduce the number of leukocyte adhesion (>74%) and TEM events (>87%) close to the control. As the first demonstration of real-time imaging of dynamic cellular events within a TEBV, this work paves the way for drug screening and disease modeling in TEBV-associated microphysiological systems.
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real time observation of leukocyte endothelium interactions in tissue Engineered Blood Vessel
Lab on a Chip, 2018Co-Authors: Zaozao Chen, Min Tang, D Huang, Weiqian Jiang, Ji Sun Park, Leigh Atchison, George A. Truskey, Kam W LeongAbstract:Human cell-based 3D tissue constructs play an increasing role in disease modeling and drug screening. Inflammation, atherosclerosis, and many autoimmune disorders involve the interactions between immune cells and Blood Vessels. However, it has been difficult to image and model these interactions under realistic conditions. In this study, we fabricated a perfusion and imaging chamber to allow the real-time visualization of leukocyte perfusion, adhesion, and migration inside a tissue-Engineered Blood Vessel (TEBV). We monitored the elevated monocyte adhesion to the TEBV wall and transendothelial migration (TEM) as the TEBV endothelium was activated by the inflammatory cytokine TNF-α. We demonstrated that treatment with anti-TNF-α or an NF-kB signaling pathway inhibitor would attenuate the endothelium activation and reduce the number of leukocyte adhesion (>74%) and TEM events (>87%) close to the control. As the first demonstration of real-time imaging of dynamic cellular events within a TEBV, this work paves the way for drug screening and disease modeling in TEBV-associated microphysiological systems.
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a tissue Engineered Blood Vessel model of hutchinson gilford progeria syndrome using human ipsc derived smooth muscle cells
Scientific Reports, 2017Co-Authors: Leigh Atchison, Haoyue Zhang, Kan Cao, George A. TruskeyAbstract:Hutchison-Gilford Progeria Syndrome (HGPS) is a rare, accelerated aging disorder caused by nuclear accumulation of progerin, an altered form of the Lamin A gene. The primary cause of death is cardiovascular disease at about 14 years. Loss and dysfunction of smooth muscle cells (SMCs) in the vasculature may cause defects associated with HGPS. Due to limitations of 2D cell culture and mouse models, there is a need to develop improved models to discover novel therapeutics. To address this need, we produced a functional three-dimensional model of HGPS that replicates an arteriole-scale tissue Engineered Blood Vessel (TEBV) using induced pluripotent stem cell (iPSC)-derived SMCs from an HGPS patient. To isolate the effect of the HGPS iSMCs, the endothelial layer consisted of human cord Blood-derived endothelial progenitor cells (hCB-EPCs) from a separate, healthy donor. TEBVs fabricated from HGPS iSMCs and hCB-EPCs show reduced vasoactivity, increased medial wall thickness, increased calcification and apoptosis relative to TEBVs fabricated from normal iSMCs or primary MSCs. Additionally, treatment of HGPS TEBVs with the proposed therapeutic Everolimus, increases HGPS TEBV vasoactivity and increases iSMC differentiation in the TEBVs. These results show the ability of this iPSC-derived TEBV to reproduce key features of HGPS and respond to drugs.
Jiansen Sun - One of the best experts on this subject based on the ideXlab platform.
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Construction of an Aptamer-SiRNA Chimera-Modified Tissue-Engineered Blood Vessel for Cell-Type-Specific Capture and Delivery.
ACS nano, 2015Co-Authors: Wen Chen, Wen Zeng, Jiansen Sun, Mingcan Yang, Ge Liu, Jingting Zhou, Jun Sun, Rui TangAbstract:The application of tissue-Engineered Blood Vessels (TEBVs) is the main developmental direction of vascular replacement therapy. Due to few and/or dysfunctional endothelial progenitor cells (EPCs), it is difficult to successfully construct EPC capture TEBVs in diabetes. RNA has a potential application in cell protection and diabetes treatment, but poor specificity and low efficiency of RNA transfection in vivo limit the application of RNA. On the basis of an acellular vascular matrix, we propose an aptamer-siRNA chimera-modified TEBV that can maintain a satisfactory patency in diabetes. This TEBV consists of two parts, CD133-adenosine kinase (ADK) chimeras and a TEBV scaffold. Our results showed that CD133-ADK chimeras could selectively capture the CD133-positive cells in vivo, and then captured cells can internalize the bound chimeras to achieve RNA self-transfection. Subsequently, CD133-ADK chimeras were cut into ADK siRNA by a dicer, resulting in depletion of ADK. An ADK-deficient cell may act as a bioreactor that sustainably releases adenosine. To reduce nonspecific RNA transfection, we increased the proportion of HAuCl4 during the material preparation, through which the transfection capacity of polyethylenimine (PEI)/polyethylene glycol (PEG)-capped gold nanoparticles (PEI/PEG-AuNPs) was significantly decreased and the ability of TEBV to resist tensile and liquid shear stress was greatly enhanced. PEG and 2'-O-methyl modification was used to enhance the in vivo stability of RNA chimeras. At day 30 postgrafting, the patency rate of CD133-ADK chimera-modified TEBVs reached 90% in diabetic rats and good endothelialization was observed.
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regulation of cellular response pattern to phosphorus ion is a new target for the design of tissue Engineered Blood Vessel
Advanced Healthcare Materials, 2015Co-Authors: Wen Chen, Wen Zeng, Jiansen Sun, Mingcan Yang, Jun Sun, Fangjuan Wang, Xiaohui Zhao, Chuhong ZhuAbstract:Dr. W. Chen, Dr. W. Zeng, Dr. J. Sun, Dr. L. Li, M. Yang, J. Sun, Dr. Y. Wu, Prof. C. Zhu Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering Key Lab for Biomechanics and Tissue Engineering of Chongqing Third Military Medical University Chongqing 400038 , China E-mail: zhuch99@yahoo.com Dr. F. Wang, Prof. X. Zhao Department of Cardiology, Xinqiao Hospital Third Military Medical University Chongqing 400038 , China E-mail: doctorzhaoxiaohui@yahoo.com
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The use of BDNF to enhance the patency rate of small-diameter tissue-Engineered Blood Vessels through stem cell homing mechanisms.
Biomaterials, 2011Co-Authors: Wen Zeng, Chunli Hou, Can Wen, Zhenhua Zhou, Wen Chen, Mingcan Yang, Jiansen SunAbstract:The patency rate of small-diameter tissue-Engineered Blood Vessels is the determinant for their application in coronary artery bypass grafting. The coronary artery is innervated by vagus nerves. The origin of vagus nerves is rich in brain-derived neurotrophic factors (BDNF). We have investigated whether BDNF could improve the patency rate of small-diameter tissue-Engineered Blood Vessels through promoting stem cell homing and paracrine activity. In vitro, we isolated early and late endothelial progenitor cells (EPCs) and found BDNF could promote single clone formation and paracrine function of EPCs, and could also induce the proliferation, migration and differentiation of late EPCs. BDNF could enhance the capturing of EPCs in parallel-plate flow chamber. Flow cytometric analysis and laser-scanning confocal microscope showed BDNF could enhance the mobilization and homing of C57BL/6 mouse EPCs after wire injury. Based on it, BDNF was coupled to the lumen surface of the Blood Vessel matrix material incubated with collagen through SPDP to construct BDNF-modified small-diameter tissue-Engineered Blood Vessel. The Blood Vessel patency rate was significantly higher than that of control group 8 weeks after implantation in rats and the endothelialization level was superior to control. These results demonstrate that BDNF can effectively improve patency of small-diameter tissue-Engineered Blood Vessels through stem cell homing and paracrine, and it is expected to play an important role in the construction of substitutes for coronary artery bypass grafting.
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The promotion of endothelial progenitor cells recruitment by nerve growth factors in tissue-Engineered Blood Vessels.
Biomaterials, 2009Co-Authors: Wen Zeng, Jiansen Sun, Wei Yuan, Can Wen, Zhenhua Zhou, Jiaqiang Xiong, Dajun YingAbstract:Endothelial progenitor cells (EPCs) mobilization and homing are critical to the development of an anti-thrombosis and anti-stenosis tissue-Engineered Blood Vessel. The growth and activation of Blood Vessels are supported by nerves. We investigated whether nerve growth factors (NGF) can promote EPCs mobilization and endothelialization of tissue-Engineered Blood Vessels. In vitro, NGF promoted EPCs to form more colonies, stimulated human EPCs to differentiate into endothelial cells, and significantly enhanced EPCs migration. Flow cytometric analysis revealed that NGF treatment increased the number of EPCs in the peripheral circulation of C57BL/6 mice. Furthermore, the treatment of human EPCs with NGF facilitated their homing into wire-injured carotid arteries after injection into mice. Decellularized rat Blood Vessel matrix was incubated with EDC cross-linked collagen and bound to NGF protein using the bifunctional coupling agent N-succinmidyl3-(2-pyridyldit-hio) propionate (SPDP). The NGF-bound tissue-Engineered Blood Vessel was implanted into rat carotid artery for 1 week and 1 month. NGF-bound Blood Vessels possessed significantly higher levels of endothelialization and patency than controls did. These results demonstrated that NGF can markedly increase EPCs mobilization and homing to vascular grafts. Neurotrophic factors such as NGF have a therapeutic potential for the construction of tissue-Engineered Blood Vessels in vivo.
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Development of anti-atherosclerotic tissue-Engineered Blood Vessel by A20-regulated endothelial progenitor cells seeding decellularized vascular matrix.
Biomaterials, 2008Co-Authors: Chuhong Zhu, Dajun Ying, Wen Zeng, Chunli Hou, Jiansen Sun, Wei Yuan, Can Wen, Wei ZhangAbstract:To investigate whether decellularized vascular tissues and A20-regulated endothelial progenitor cells can be used for constructing a transgenic tissue-Engineered Blood Vessel with anti-atherosclerotic vascular stenotic properties. A20 gene-transfected endothelial progenitor cells differentiated endothelial cells and smooth muscle cells attached to and migrated into the decellularized porcine vascular scaffolding in a bioreactor. The histology of the conduits revealed viable and layered tissue. Scanning electron microscopy showed confluent, homogeneous tissue surfaces. The mechanical strength of the pulsed constructs was similar to that of the human artery. In vivo, the A20 gene-transfected tissue-Engineered Blood Vessels were transplanted into the carotid artery of a rat for 6 months. Blood Vessel xenotransplantation caused hyperacute rejection; all transplanted control Blood Vessels were completely rejected, but A20-transfected tissue-Engineered Blood Vessels demonstrated good flow on implantation, and remained open for 6 months postoperatively, as assessed by Doppler. The HE stain demonstrated that the Vessels were patent, without evidence of stenosis or dilatation after 6 months. These results demonstrate that transgenic tissue-Engineered Blood Vessels have long-term patency and unique anti-stenotic properties.
Mingcan Yang - One of the best experts on this subject based on the ideXlab platform.
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Construction of a small-caliber tissue-Engineered Blood Vessel using icariin-loaded β-cyclodextrin sulfate for in situ anticoagulation and endothelialization
Science China. Life sciences, 2018Co-Authors: Jingyuan Yang, Da Huo, Keyu Wei, Yeqin Wang, Ning Ding, Tianran Wang, Guanyuan Yang, Mingcan YangAbstract:The rapid endothelialization of tissue-Engineered Blood Vessels (TEBVs) can effectively prevent thrombosis and inhibit intimal hyperplasia. The traditional Chinese medicine ingredient icariin is highly promising for the treatment of cardiovascular diseases. β-cyclodextrin sulfate is a type of hollow molecule that has good biocompatibility and anticoagulation properties and exhibits a sustained release of icariin. We studied whether icariin-loaded β-cyclodextrin sulfate can promote the endothelialization of TEBVs. The experimental results showed that icariin could significantly promote the proliferation and migration of endothelial progenitor cells; at the same time, icariin could promote the migration of rat vascular endothelial cells (RAVECs). Subsequently, we used an electrostatic force to modify the surface of the TEBVs with icariin-loaded β-cyclodextrin sulfate, and these Vessels were implanted into the rat common carotid artery. After 3 months, micro-CT results showed that the TEBVs modified using icariin-loaded β-cyclodextrin sulfate had a greater patency rate. Scanning electron microscopy (SEM) and CD31 immunofluorescence results showed a better degree of endothelialization. Taken together, icariin-loaded β-cyclodextrin sulfate can achieve anticoagulation and rapid endothelialization of TEBVs to ensure their long-term patency.
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exosome modified tissue Engineered Blood Vessel for endothelial progenitor cell capture and targeted sirna delivery
Macromolecular Bioscience, 2018Co-Authors: Wen Chen, Mingcan Yang, Jian Bai, Xiangrui Kong, Yu Gao, Li Xiao, Bingyi ShiAbstract:Instability and poor targeting causes the long-term patency of RNA-modified tissue engineering Blood Vessels (TEBVs) remaining unsatisfactory. RNA can be enriched in exosome and then delivered into targeted cells while whether exosome-modified TEBVs achieve RNA targeted delivery is unclear. Here, to promote the expression of klotho protein on the mesenchymal stem cell (MSC)-derived exosomes, klotho plasmids are first transfected into MSCs, and adenosine kinase (ADK) siRNA is then loaded into exosome (klotho/ADK siRNA-exosome) using electrotransfection. Flow chamber results show that klotho/ADK siRNA-exosome can effectively capture circulating endothelial progenitor cells (EPCs). Besides, the captured EPCs can endocytose this exosome, and then decompose it into klotho protein and ADK siRNA. Moreover, ADK siRNA promotes the paracrine of proangiogenic factors and adenosine from EPCs, which further facilitate proliferation and migration of endothelial cells. Based on polyethyleneimine-capped gold nanoparticles, exosome-modified TEBVs are constructed through layer-by-layer assembly. Animal experimental results show that klotho/ADK siRNA-exosome-modified TEBVs can maintain the patency up to one month, and good endothelialization is observed. In short, one exosome-modified TEBV is constructed, capture molecules on the surface of exosome capture the circulating EPCs, and the loaded RNA achieves its purpose of accurate treatment depending on the needs of patients.
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Construction of Antithrombotic Tissue-Engineered Blood Vessel via Reduced Graphene Oxide Based Dual-Enzyme Biomimetic Cascade
ACS nano, 2017Co-Authors: Da Huo, Mingcan Yang, Ge Liu, Yuxin Wang, Ge Guan, Keyu Wei, Jingyuan Yang, Lingqin ZengAbstract:Thrombosis is one of the biggest obstacles in the clinical application of small-diameter tissue-Engineered Blood Vessels (TEBVs). The implantation of an unmodified TEBV will lead to platelet aggregation and further activation of the coagulation cascade, in which the high concentration of adenosine diphosphate (ADP) that is released by platelets plays an important role. Inspired by the phenomenon that endothelial cells continuously generate endogenous antiplatelet substances via enzymatic reactions, we designed a reduced graphene oxide (RGO) based dual-enzyme biomimetic cascade to successively convert ADP into adenosine monophosphate (AMP) and AMP into adenosine. We used RGO as a support and bound apyrase and 5′-nucleotidase (5′-NT) on the surface of RGO through covalent bonds, and then, we modified the surface of the collagen-coated decellularized vascular matrix with the RGO-enzyme complexes, in which RGO functions as a platform with a large open surface area and minimal diffusion barriers for substrates...
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Construction of an Aptamer-SiRNA Chimera-Modified Tissue-Engineered Blood Vessel for Cell-Type-Specific Capture and Delivery.
ACS nano, 2015Co-Authors: Wen Chen, Wen Zeng, Jiansen Sun, Mingcan Yang, Ge Liu, Jingting Zhou, Jun Sun, Rui TangAbstract:The application of tissue-Engineered Blood Vessels (TEBVs) is the main developmental direction of vascular replacement therapy. Due to few and/or dysfunctional endothelial progenitor cells (EPCs), it is difficult to successfully construct EPC capture TEBVs in diabetes. RNA has a potential application in cell protection and diabetes treatment, but poor specificity and low efficiency of RNA transfection in vivo limit the application of RNA. On the basis of an acellular vascular matrix, we propose an aptamer-siRNA chimera-modified TEBV that can maintain a satisfactory patency in diabetes. This TEBV consists of two parts, CD133-adenosine kinase (ADK) chimeras and a TEBV scaffold. Our results showed that CD133-ADK chimeras could selectively capture the CD133-positive cells in vivo, and then captured cells can internalize the bound chimeras to achieve RNA self-transfection. Subsequently, CD133-ADK chimeras were cut into ADK siRNA by a dicer, resulting in depletion of ADK. An ADK-deficient cell may act as a bioreactor that sustainably releases adenosine. To reduce nonspecific RNA transfection, we increased the proportion of HAuCl4 during the material preparation, through which the transfection capacity of polyethylenimine (PEI)/polyethylene glycol (PEG)-capped gold nanoparticles (PEI/PEG-AuNPs) was significantly decreased and the ability of TEBV to resist tensile and liquid shear stress was greatly enhanced. PEG and 2'-O-methyl modification was used to enhance the in vivo stability of RNA chimeras. At day 30 postgrafting, the patency rate of CD133-ADK chimera-modified TEBVs reached 90% in diabetic rats and good endothelialization was observed.
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regulation of cellular response pattern to phosphorus ion is a new target for the design of tissue Engineered Blood Vessel
Advanced Healthcare Materials, 2015Co-Authors: Wen Chen, Wen Zeng, Jiansen Sun, Mingcan Yang, Jun Sun, Fangjuan Wang, Xiaohui Zhao, Chuhong ZhuAbstract:Dr. W. Chen, Dr. W. Zeng, Dr. J. Sun, Dr. L. Li, M. Yang, J. Sun, Dr. Y. Wu, Prof. C. Zhu Department of Anatomy, National & Regional Engineering Laboratory of Tissue Engineering Key Lab for Biomechanics and Tissue Engineering of Chongqing Third Military Medical University Chongqing 400038 , China E-mail: zhuch99@yahoo.com Dr. F. Wang, Prof. X. Zhao Department of Cardiology, Xinqiao Hospital Third Military Medical University Chongqing 400038 , China E-mail: doctorzhaoxiaohui@yahoo.com