Development of a novel tissue engineered model of the cerebrovasculature
University of British Columbia
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. Although scientists realize that understanding how to keep blood vessels in the brain healthy may offer new ways to treat brain disorders including Alzheimer’s Disease (AD), a big challenge 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, we now will adapt 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.
Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging
The present work might accelerate the development of therapeutics for multiple neurodegenerative disease of aging in various ways. Our novel human-based platform of the brain vessel can be deployed along with mechanistic/inquiry arms as well as therapeutic screening/development arms. Examples of the former include discovery and validation of pathways that regulate human blood brain barrier integrity and inflammation, which may be relevant to several neurodegenerative disease of aging including stroke as well as to acute conditions including brain injury and cancer. Examples of the latter include the ability to evaluate compounds for their predicted human response in an experimental setting, thereby potentially improving our predictive power of preclinical studies. A validated human-based model system amenable to mechanistic studies will therefore complement in vivo studies toward the identification of novel pathways and potential therapeutic targets and accelerate the discovery and translation of therapies.
During the time of the funding we anticipate to develop a novel and highly innovative human-based brain blood vessel equivalent. This model will help us to better understand how Alzheimer’s Disease affects blood vessel and how lipoproteins which are molecule carrying lipids in the body influence blood vessel functions in the context of Alzheimer disease.