Tissue Engineering of Blood Vessel

Endothelial cells line blood vessels and regulate the passage of cells from the circulation into the tissues. This is an important 'gate keeper' function allows them to regulate many physiological and disease processes. However, this is a very dynamic process with circulating cells only interacting with endothelial under conditions of flow. Most studies of how cells interact with the endothelial lining of blood vessels are only performed under static conditions but this does not replicate what happens in life. Scientists at the Centre for Biomaterials and Tissue Engineering have therefore developed systems for studying how cells interact with the endothelial cells under conditions of flow and are using these to study a number of important disease processes.
Cancer cell binding to endothelium
Many cancers metastasise to other sites in the body. To do this, after entering the circulation, tumour cells must bind to the endothelial lining of blood vessels in order to leave the circulation and form a metastatic deposit in the tissues. This is an active process that involves the interaction of ligands on the cancer cells with adhesion molecules on the endothelium. Using flow systems we can study how different tumour cells bind to the endothelial lining of blood vessels and leave the circulation to form new cancer deposits. These studies enable us to identify markers for cancers that are more likely to metastasise and treatments that could prevent metastasis.
Right: Two looped movie clips showing fluorescently labelled cancer cells flowing over the endothelial lining of a blood vessels just as they would in the circulation. The cells in the top-most movie are from a cancer that metastasises and express a ligand that enables them to adhere to the endothelial cells. Whilst the cancer cells in the bottom movie do not express this ligand and are unable to adhere or metastasise.
Candida adhesion to endothelium
Circulating microorganisms, including bacteria and fungi, also have to bind to the endothelial lining of blood vessels in order to leave the circulation and infect the tissues. Candida albicans, is a fungal organism that is a major cause of death in patients who are immunocompromised or being treated in intensive care units. These patients are susceptible to systemic infection with this organism and once it leaves the circulation, it can cause massive tissue destruction. The mechanisms by which the organism adheres to the endothelial lining of blood vessels and invades the tissues is not known and we are using flow systems to study how Candida interacts with endothelial cells under conditions of flow.