Critical appraisal of the chorioallantoic membrane model for studying angiogenesis in preclinical research

Angiogenesis, the biological mechanism by which new blood vessels are generated from existing ones, plays a vital role in growth and development. Effective preclinical screening is necessary for the development of medications that may enhance or inhibit angiogenesis in the setting of different disorders. Traditional in vitro and, in vivo models of angiogenesis are laborious and time-consuming, necessitating advanced infrastructure for embryo culture.

A challenge encountered by researchers studying angiogenesis is the lack of appropriate techniques to evaluate the impact of regulators on the angiogenic response. An ideal test should possess reliability, technical simplicity, easy quantifiability, and, most importantly, physiological relevance. The CAM model, leveraging the extraembryonic membrane of the chicken embryo, offers a unique combination of accessibility, low cost, and rapid development, making it an attractive option for angiogenesis assays. This review evaluates the strengths and limitations of the CAM model in the context of its anatomical and physiological properties, and its relevance to human pathophysiological conditions. Its abundant capillary network makes it a common choice for studying angiogenesis. The CAM assay serves as a substitute for animal models and offers a natural setting for developing blood vessels and the many elements involved in the intricate interaction with the host. Despite its advantages, the CAM model's limitations are notable. These include species-specific responses that may not always extrapolate to humans and the ethical considerations of using avian embryos. We discuss methodological adaptations that can mitigate some of these limitations and propose future directions to enhance the translational relevance of this model. This review underscores the CAM model's valuable role in angiogenesis research and aims to guide researchers in optimizing its use for more predictive and robust preclinical studies.

The highly vascularized chorioallantoic membrane (CAM) of fertilized chicken eggs is a cost-effective and easily available method for screening angiogenesis, in comparison to other animal models.