Engineered Artery Growth in Vitro Based on Cell-Remodeled Fibrin

基于细胞重塑纤维蛋白的体外工程动脉生长

基本信息

  • 批准号:
    7878734
  • 负责人:
  • 金额:
    $ 83.06万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2006
  • 资助国家:
    美国
  • 起止时间:
    2006-06-01 至 2012-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The ultimate goal of this project is a completely biological artificial artery (bioartificial artery) that is suitable as a small diameter vascular graft, such as for use in coronary bypass. We will build upon our two major discoveries: (1) when neonatal smooth muscle cells (SMCs) are entrapped in fibrin gel formed as a tube around a nonadhesive rod, the SMCs contract the gel around the rod, causing the fibrin fibrils and SMCs to become circumferentially aligned. As the SMCs subsequently degrade the fibrin, they produce extensive cross-linked collagen and elastic fibers, which also are circumferentially aligned. This remodeling provides the construct with tensile mechanical properties approaching values of arterial tissue; (2) endothelial cells cultured from blood can be expanded to 10A8 cells in less than six weeks, the expansion occurring from a putative circulating marrow-derived angioblast. In Specific Aim 1, we will compare the properties of remodeled fibrin gel tubes prepared with neonatal SMCs (rat, pig, and human) under the static culture condition used to date with tubes subject to cyclic distension, imparting a mechanical signal expected to increase tissue growth as we found in collagen gel-based tubes, and controlled transmural flow of culture medium, minimizing gradients of soluble factors and potentially leading to increased and near-uniform tissue growth. In Aim 2, we will study the properties of bioartificial arteries, the remodeled fibrin/SMC constructs described above plus an endothelium generated using traditional late-stage seeding of the tubular construct with the blood outgrowth endothelial cells (BOECs) noted above, including their adhesion strength in pulsatile flow at physiological shear stress and their state of activation. Once such constructs have been validated in vitro we will proceed with testing the viability, patency, and hemocompatibility properties in animal models. The bioartificial artery will be implanted into the aorta of the rat, first in the syngeneic setting and subsequently in the "allogeneic" setting (with respect to the SMCs; autologous BOECs will be used). A similar allogeneic study will subsequently be performed in the pig. We will also fabricate bioartificial arteries from human SMC and BOECs, so that these results should be directly relevant for a future clinical study.
描述(由申请人提供): 该项目的最终目标是完全生物化的人工动脉(生物人工动脉),适合作为小直径血管移植物,例如用于冠状动脉搭桥术。我们将建立在我们的两个重大发现的基础上:(1)当新生儿平滑​​肌细胞(SMC)被包裹在纤维蛋白凝胶中时,纤维蛋白凝胶形成为围绕非粘性棒的管子,SMC使棒周围的凝胶收缩,导致纤维蛋白原纤维和SMC变得沿圆周对齐。当 SMC 随后降解纤维蛋白时,它们会产生广泛的交联胶原蛋白和弹性纤维,这些纤维也沿圆周排列。这种重塑为结构提供了接近动脉组织值的拉伸机械性能; (2)从血液中培养的内皮细胞可以在不到六周的时间内扩增为10A8细胞,扩增发生在假定的循环骨髓来源的成血管细胞中。在具体目标 1 中,我们将比较在静态培养条件下用新生儿 SMC(大鼠、猪和人)制备的重构纤维蛋白凝胶管与经受周期性扩张的管的特性,从而传递预期增加组织的机械信号我们在基于胶原凝胶的管中发现了生长,并控制了培养基的跨壁流动,最大限度地减少了可溶性因子的梯度,并可能导致组织生长增加且接近均匀。在目标 2 中,我们将研究生物人工动脉、上述重构的纤维蛋白/SMC 结构以及使用上述血液生长内皮细胞 (BOEC) 的管状结构的传统后期接种生成的内皮细胞的特性,包括它们的粘附生理剪切应力下脉动流的强度及其激活状态。一旦此类结构在体外得到验证,我们将继续在动物模型中测试其活力、通畅性和血液相容性。生物人工动脉将被植入大鼠的主动脉,首先在同基因环境中,然后在“同种异体”环境中(相对于SMC;将使用自体BOEC)。随后将在猪身上进行类似的同种异体研究。我们还将利用人类 SMC 和 BOEC 制造生物人工动脉,因此这些结果应该与未来的临床研究直接相关。

项目成果

期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Combating Adaptation to Cyclic Stretching By Prolonging Activation of Extracellular Signal-Regulated Kinase.
  • DOI:
    10.1007/s12195-013-0289-4
  • 发表时间:
    2013-09
  • 期刊:
  • 影响因子:
    2.8
  • 作者:
    Weinbaum, Justin S.;Schmidt, Jillian B.;Tranquillo, Robert T.
  • 通讯作者:
    Tranquillo, Robert T.
Transmural flow bioreactor for vascular tissue engineering.
  • DOI:
    10.1002/bit.22475
  • 发表时间:
    2009-12-15
  • 期刊:
  • 影响因子:
    3.8
  • 作者:
    Bjork, Jason W.;Tranquillo, Robert T.
  • 通讯作者:
    Tranquillo, Robert T.
Implantable arterial grafts from human fibroblasts and fibrin using a multi-graft pulsed flow-stretch bioreactor with noninvasive strength monitoring.
  • DOI:
    10.1016/j.biomaterials.2010.09.019
  • 发表时间:
    2011-01
  • 期刊:
  • 影响因子:
    14
  • 作者:
    Syedain, Zeeshan H.;Meier, Lee A.;Bjork, Jason W.;Lee, Ann;Tranquillo, Robert T.
  • 通讯作者:
    Tranquillo, Robert T.
Blood outgrowth endothelial cells alter remodeling of completely biological engineered grafts implanted into the sheep femoral artery.
  • DOI:
    10.1007/s12265-013-9539-z
  • 发表时间:
    2014-03
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Meier, Lee A.;Syedain, Zeeshan H.;Lahti, Matthew T.;Johnson, Sandra S.;Chen, Minna H.;Hebbel, Robert P.;Tranquillo, Robert T.
  • 通讯作者:
    Tranquillo, Robert T.
Monitoring collagen transcription by vascular smooth muscle cells in fibrin-based tissue constructs.
监测基于纤维蛋白的组织结构中血管平滑肌细胞的胶原蛋白转录。
  • DOI:
    10.1089/ten.tec.2009.0112
  • 发表时间:
    2010
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Weinbaum,JustinS;Qi,Jie;Tranquillo,RobertT
  • 通讯作者:
    Tranquillo,RobertT
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ROBERT T TRANQUILLO其他文献

ROBERT T TRANQUILLO的其他文献

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{{ truncateString('ROBERT T TRANQUILLO', 18)}}的其他基金

Biologically-engineered Transcatheter Vein Valve: Design Optimization and Preclinical Testing
生物工程经导管静脉瓣膜:设计优化和临床前测试
  • 批准号:
    10594865
  • 财政年份:
    2023
  • 资助金额:
    $ 83.06万
  • 项目类别:
Completely biological tissue-engineered pulmonic valve grown in vitro from human
从人体体外培养的完全生物组织工程肺动脉瓣
  • 批准号:
    8083856
  • 财政年份:
    2011
  • 资助金额:
    $ 83.06万
  • 项目类别:
Completely biological tissue-engineered pulmonic valve grown in vitro from human cells for pediatric patients
完全生物组织工程肺动脉瓣,由人体细胞在体外培养,供儿科患者使用
  • 批准号:
    10188591
  • 财政年份:
    2011
  • 资助金额:
    $ 83.06万
  • 项目类别:
Biopolymer-guided human stem cell assembly for engineered myocardium
生物聚合物引导的人类干细胞组装用于工程化心肌
  • 批准号:
    8328585
  • 财政年份:
    2011
  • 资助金额:
    $ 83.06万
  • 项目类别:
Perfusable and beating engineered myocardium from human progenitor cells based on
基于人类祖细胞的可灌注和跳动工程心肌
  • 批准号:
    8138261
  • 财政年份:
    2011
  • 资助金额:
    $ 83.06万
  • 项目类别:
Tissue-engineered pulmonic valve grown from human cells for pediatric patients
由人体细胞培育而成的组织工程肺动脉瓣,供儿科患者使用
  • 批准号:
    8527302
  • 财政年份:
    2011
  • 资助金额:
    $ 83.06万
  • 项目类别:
Completely biological tissue-engineered pulmonic valve grown in vitro from human cells for pediatric patients
完全生物组织工程肺动脉瓣,由人体细胞在体外培养,供儿科患者使用
  • 批准号:
    9520733
  • 财政年份:
    2011
  • 资助金额:
    $ 83.06万
  • 项目类别:
Tissue-engineered pulmonic valve grown from human cells for pediatric patients
由人体细胞培育而成的组织工程肺动脉瓣,供儿科患者使用
  • 批准号:
    8649073
  • 财政年份:
    2011
  • 资助金额:
    $ 83.06万
  • 项目类别:
Tissue-engineered pulmonic valve grown from human cells for pediatric patients
由人体细胞培育而成的组织工程肺动脉瓣,供儿科患者使用
  • 批准号:
    8242099
  • 财政年份:
    2011
  • 资助金额:
    $ 83.06万
  • 项目类别:
Biopolymer-guided human stem cell assembly for engineered myocardium
生物聚合物引导的人类干细胞组装用于工程化心肌
  • 批准号:
    8529260
  • 财政年份:
    2011
  • 资助金额:
    $ 83.06万
  • 项目类别:

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用于连续监测心力衰竭生物标志物的无试剂传感器技术
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