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.
| Guedez, Liliana; Rivera, Alexandra M; Salloum, Rita et al. (2003) Quantitative assessment of angiogenic responses by the directed in vivo angiogenesis assay. Am J Pathol 162:1431-9 |
