Development of a Novel Tissue Engineered Model of the Cerebrovasculature
Principal Investigator
Mentors
Project Goals
With every heartbeat, one quarter of all the blood in the body flows through the brain, and this activity is essential to keep neurons in the brain healthy throughout life. Scientists have long understood that keeping blood vessels in the brain healthy may offer new ways to treat brain disorders, including Alzheimer’s disease (AD). A big challenge, however, is that there are not many methods to study the brain’s blood vessels outside of an animal model, and animals models may not always mimic the human condition closely enough to provide answers that help to develop effective treatments for dementia. We have made considerable progress in being able to grow functional three dimensional human-derived blood vessels in the test tube using “tissue engineering” technology, and are now focused on adapting this technology to make brain blood vessels that mimic those in the human brain. Our technologies will be used to rapidly test several questions about how these vessels become damaged in AD and how to prevent or repair this damage.
Project Summary
We are developing novel methods to analyze in the test tube the importance of the brain vessels in the development of AD.
Our first aim is to develop a model of the large blood brain vessels using different types of cells, namely astrocytes, smooth muscle and endothelial cells, in a process known as tissue engineering. Alzheimer's patients suffer from aggregated forms of amyloid beta protein (Aβ) within the brain, as well as in their brain vessels. In order to mimic this pathology, we will inject Aβ within our engineered vessel and analyze the function of the tissues. In the second aim we are developing a model of small blood vessels in the brain, named capillaries. To do this, we are using special cell culture devices (microfluidic chips) enabling the cell to growth in three-dimensional organization mimicking capillaries. Same as with the first aim, we plan to further analyze the effects of Aβ on these structures.
Numerous scientists have agreed that we need a better understanding the role of the brain vessels in the pathology of AD, and in recent years that’s been emphasized as a priority topic. However a critical roadblock to progress in this topic is the lack of appropriate models. Our proposal is a direct answer to this roadblock and is therefore particularly innovative. Our research will permit to better understand the role of the brain vessels in AD and therefore to develop specific treatments.
Publications
Button EB, Gilmour M, Cheema HK, Martin EM, Agbay A, Robert J, Wellington CL. Vasoprotective Functions of High-Density Lipoproteins Relevant to Alzheimer's Disease Are Partially Conserved in Apolipoprotein B-Depleted Plasma. Int J Mol Sci. 2019 Jan 22;20(3). pii: E462. doi: 10.3390/ijms20030462. PubMed PMID: 30678190. 
First published on: July 10, 2015
Last modified on: November 18, 2024