Implantable Capsule For Quantitative Angiogenesis Studie

本研究的目的是开发一种可植入的胶囊，用于研究促进和抑制小鼠体内血管生成。所采用的方法采用一端密封的管状胶囊。胶囊将填充有商业细胞外基质凝胶（例如，基质胶），其含有血管生成剂，如碱性成纤维细胞生长因子和肝素。选择胶囊配置作为在植入部位扩散释放到相邻组织的结果，在胶囊内产生毫米距离内药剂空间梯度的手段。主要用途是评估对释放物质的血管生成反应的方面，例如迁移到胶囊中的细胞的特征和组织的空间变化，以及参与细胞表达的基因。另外的应用包括研究由添加到胶囊中或以其他方式施用给宿主动物的抑制剂（例如金属蛋白酶组织抑制剂2（TIMP 2）和TNP-470）产生的血管生成反应的改变。用于定量胶囊内血管形成的措施是测定胶囊回收前静脉注射的异硫氰酸荧光素（FITC）-葡聚糖的滞留量。

The goal of this project is to develop an implantable capsule for studying the promotion and inhibition of angiogenesis in vivo in mice. The approach being pursued employs a tubular capsule sealed at one end. The capsule will be filled with a commercial extracellular matrix gel (e.g., Matrigel) containing angiogenic agents, such as basic fibroblast growth factor and heparin. The capsule configuration was chosen as a means for generating a spatial gradient of the agents within the capsule over a distance of millimeters as a result of diffusional release to the adjacent tissue at the implant site. A primary use is in evaluating aspects of the angiogenic response to the released substances, such as the spatial variation in the characteristics and organization of the cells that migrate into the capsules, and the genes expressed by the participating cells. Additional applications include study of alterations in the angiogenic response produced by inhibitors added to the capsules or otherwise administered to the host animal, such as Tissue Inhibitor of Metalloproteinase 2 (TIMP2) and TNP-470. A measure employed for quantifying vascularization within the capsule is to assay the contents for detention of fluorescein isothiocyanate (FITC)-dextran that is injected intravenously prior to capsule recovery.