Implantable Capsule For Quantitative Angiogenesis Studie

本项目的目标是开发一种可植入的胶囊，用于研究小鼠体内血管生成的促进和抑制作用。所采用的方法采用一端密封的管状胶囊。胶囊将填充商业细胞外基质凝胶（例如，Matrigel），其中含有血管生成剂，如碱性成纤维细胞生长因子和肝素。选择胶囊结构作为一种手段，用于在胶囊内产生药物在毫米距离上的空间梯度，因为扩散释放到植入部位的邻近组织。主要用途是评估血管生成对释放物质的反应，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。其他应用包括研究添加到胶囊中或以其他方式给宿主动物的抑制剂（如组织金属蛋白酶2抑制剂（TIMP2）和TNP-470）产生的血管生成反应的改变。定量胶囊内血管形成的一种方法是测定在胶囊回收前静脉注射的异硫氰酸荧光素-葡聚糖的滞留含量。

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.