Human Microvessel Culture System (hMCS) Angiogenesis-targeting therapies, either inhibiting or promoting new vessel growth, have the potential for treating numerous diseases including cancer, eye diseases, cardiac and peripheral vascular disease, skin disorders, fibro-proliferative diseases, and inflammatory conditions such as arthritis. Furthermore, growing evidence indicates that for many of these diseases combinations of agents targeting multiple different vascular activities are proving more efficacious. As demand and complexity increases for these therapies, there is a growing need for more informative assays of relevant vascular growth and stability. Ideally, such an assay should recapitulate as much of the in vivo biological process as possible, while maintaining experimental simplicity and cost effectiveness. Angiomics, Inc. was founded on proven technology based on the manipulation and culturing of isolated microvessels from a variety of tissues. Utilizing rodent sources, this microvessel culture system has been used extensively and effectively as a more comprehensive experimental and discovery platform for a variety of vascular-related activities and therapies. Because the system utilizes intact microvessels, angiogenesis is more accurately recapitulated in both the culture and in vivo settings. In this system, true neovessels sprout and grow from intact microvessels within a 3-D matrix environment. Consequently, all angiogenesis-relevant activities/elements including perivascular cell behavior are present and integrated in the assay. The overall objective of this proposal is to adapt this proven and versatile microvessel culture system to support human microvessel viability and activity to add utility and value to the platform. It is guided by two Objectives tha 1) identify media components, guided by the rodent system, and 2) evaluate combinations of candidate growth factors or hypoxia factors that will support human microvessel viability and angiogenesis in culture.
Public Health Relevance Statement: Public Health Relevance: Human Microvessel Culture System (hMCS) Comprehensive yet readily performed in vitro angiogenesis assays are needed as the demand for more complex vascular-targeting therapies rises. This project will adapt a proven experimental platform involving 3-D cultures of isolated microvessels to utilize human microvessels thereby expanding its utility to include the research and development of new and complex vascular-targeting drug therapies.
Project Terms: 3-Dimensional; angiogenesis; Angiopoietin-1; Angiopoietin-2; Arthritis; autocrine; base; Biological Assay; Biological Process; Blood Vessels; Cardiac; cell behavior; Coculture Techniques; Complex; Conditioned Culture Media; cost effectiveness; Data; Disease; efficacy testing; Elements; Environment; Experimental Models; Eye diseases; Fractionation; Growth; Growth Factor; Hepatocyte Growth Factor; Human; Hypoxia; Implant; In Vitro; in vivo; Inflammatory; Investigation; Malignant Neoplasms; Mediating; member; Mus; Oxygen; paracrine; Pericytes; Peripheral Vascular Diseases; Pharmacotherapy; Phase; pre-clinical; Proteins; Proteomics; public health relevance; Rattus; Reagent; research and development; research study; response; Rodent; Role; skin disorder; Source; Stromal Cells; System; Technology; Testing; Tissues; Vascular Endothelial Growth Factors
