The process of new blood vessel formation
The growth and development of new tissue in vivo requires adequate transport of nutrients
to the tissue and removal of waste products. When new tissue is small (i.e. less than 1-2
mm diameter) local diffusion will provide sufficient mass transport to and from the site.
Upon further growth, the requirements for mass transport exceed the capacity of diffusive
flux, so a blood supply must be developed for the new tissue. The process of creating a
stable blood source is known as angiogenesis and is mediated by many molecular entities
defined as angiogenic factors.
Angiogenesis is required in tissue engineering of replacement tissues and organs to insure
the new tissue has adequate blood supply for mass transport to promote adaptation and
viability of the engineered tissue in the patient. For cases of undesired tissue growth in
cancerous tumors and synovial pannus formation in rheumatoid arthritis, inhibition of
angiogenesis is a major clinical goal. Therefore, the discovery of molecular mediators of
angiogenesis and understanding the relationships between these angiogenic factors is
critical to developing successful strategies to either enhance or inhibit angiogenesis.
Investigation of angiogenesis at GlycoTech involves the use of multiple in vitro and in
vivo assays. The complexity of the angiogenic process suggests that no single assay is
adequate to serve as a complete model of angiogenesis for the purpose of developing new
and novel therapeutic strategies.
Since angiogenesis is the process of developing new blood vessels, the assays involve the
formation of new vessels dominated by the migration and organization of endothelial cells.
This behavior of the endothelial cells to form new tubules is monitored by visualization
through a microscope for the various assay formats. Our inverted stage microscope with
large working distance and equipped with bright field, phase contrast, and epifluorescent
optics allows flexibility in selectition of tissue culture plates and optical mode to
obtain the best visualization of cell behavior. Assays dependent on direct visualization
to record results can be quite subjective by different individuals, so we utilize digital
imaging to standardize and quantify the assays for determining the effect of individual
agents on the angiogenic process. A schematic of the laboratory is shown on the next page.