A novel combination of growth factors that may serve as a basis for promoting blood vessel formation in vitro as well as promoting of the investment of those vessels with smooth muscle cells.

BACKGROUND: Early concept stage screening of compounds for potential therapeutic application is a critical stage in drug development and represents a market of over USD$1.2B/yr.  It is estimated that cell-based and HCS assays represented approximately $560 million in sales in 2007. Cell based assays are emerging as an alternative to HTS as they provide a closer representation of actual tissues, provide the flexibility of being able to evaluate a number of diverse cellular outcomes simultaneously, and allow one to examine specificity and functionality.  The natural evolution of cell based screening is the formation of tissue engineered multicellular systems that better mimic the complex interactions of multiple cell types and the impact of a potential therapeutic on a pseudo tissue system.  To be effective, these assays must be relatively simple, reproducible, and relevant to the system to be evaluated. Similarly, while social pressure in Europe and Asia call to reduce the application of animals for biomedical research purposes, it has been estimated that 80% of the animals used for toxicology testing could potentially be replaced by tissue engineered products.

 

The difficulty in generating complex functional blood vessels in vitro has been an important limitation to the adoption and application of complex cell based models for functional screening and drug discovery.  While the formation of endothelial tubes is well known within the academic literature, the ability to generate integrated vessels that contain vascular endothelial cells, associated smooth muscle cells, and demonstrate vasoreactivity has been elusive.  Similarly, the generation of stable, secure and invested blood vessels has been a challenge for tissue engineers, 2D and 3D cell-based assay developers, and those considering regenerative medicine strategies employing stem and progenitor cells seeding within biomaterials.  The ability to develop a system for self-assembling relevant cell types into stable, reactive blood vessels in vitro would allow for the discovery of factors affecting vasculogenesis and subsequent angiogenesis as well as screen compounds for their ability to affect such processes.

 

DESCRIPTION OF THE INVENTION: A leading cardiovascular scientist at Robarts has identified a novel combination of growth factors that may serve as a basis for promoting blood vessel formation in vitro as well as promoting of the investment of those vessels with smooth muscle cells.  The formation of complex blood vessels have been demonstrated in 2D models and the establishment of reactive vessels evaluated in 3D models.  The growth factors combination provides a strong method of supporting either vasculogenesis or angiogenesis in culture.  Together this may provide a foundation for the generation of simple or complex tissue equivalent models for the screening of angiogenic compounds or potential side effects of compounds on blood vessel structure.

 

POTENTIAL ADVANTAGES/USES:

• Technology based upon developmental processes associated with angiogenesis
• Growth factor system specific to stabilization of vessels
• Allows for the generation of model systems of vasculogenesis and angiogenesis
• Can facilitate self assembly of vessels within on-demand tissue equivalents
• Reactive vessels will allow for functional screening of vessel activity in addition to angiogenesis
• Direct application as cell based research tool for discovering factors critical for angiogenesis
• May serve as in vitro assay for screening the impact of cosmetic, ophthalmic, and therapeutic factors upon angiogenesis and vessel stability

 

Keywords: blood vessels, supplements, vasculogenesis, vascular endothelial cells, smooth muscle cells, growth factors, cell culture, in vitro models, cell based models, 3D cell models, tissue equivalents, angiogenesis

 

Preclinical

Provisional Phase Application