Development of a model of invivo angiogenesis : murine subutaneous matrigel sac model

Angiogenesis, the formation of new blood vessels, has become a broad subject and is a very active area for current research. It has a pivotal role in many disease processes. The disturbance of the fine balance of vascularity in the body, is the pathological basis for these diseases. Angiogenesis assays are an important tool for studying both the mechanisms of angiogenesis and the potential development of therapeutic strategies to modulate neovascularisation. In-vivo angiogenesis assays are considered to be the most informative of these but are often expensive, time consuming and require specialist training to perform. The main technical challenge in any study of angiogenesis is the selection of the most appropriate assay. The ideal angiogenesis assay would be robust, rapid, and reproducible with reliable readouts, automated computational analysis, and multi-parameter assessment, including positive and negative controls and should relate directly to results seen in the clinic. Despite the increasing numbers of both in vitro and in vivo assays, a 'gold-standard' angiogenesis assay has yet to be developed. Objectives of this research project was to develop an in-vivo angiogenesis assay which is both inexpensive and technically less demanding for quantification of compounds that affect angiogenesis. This thesis includes the process of developing the model, which started off from an air sac in a rodent model and evolved into a subcutaneous matrigel sac model. The subcutaneous fibrous sac which was injected with matrigel treated with bFGF at 100ng/{u03BC}l generated angiogenesis which could be measured and modulated. After establishment ofthe model it was tested with both pro and anti angiogenic compounds with known in vitro and in vivo activity. The results of these tests are encouraging as the model has reproduced anticipated results. Thus we have developed an in-expensive assay which is not technically demanding and enables the researcher to access angiogenesis over differing time points, trial pro- and antiangiogenic compounds and cell lines, in a matrix which is of a consistent shape and initially devoid of vessels. The next set of experiments includes more experiments with angiogenic modulators and also to test substances of unknown in vivo angiogenic potential