New Ways to investigate Dementia made possible through Engineered Human Cerebral Blood Vessels

Dr. Cheryl Wellington

“While the role of the brain’s blood vessels is increasingly recognized in dementia research, models that capture the normal functioning that occurs in human brains are lacking. In an effort to fill this gap, my lab bioengineered a human vascular model. Scientists will be able to use it to answer basic to translational research questions, and develop new drugs.” Dr. Cheryl Wellington

 

With each heartbeat, one quarter of the body’s blood supply flows to the brain.

 

This process – known as cerebral blood flow – delivers oxygen, simple sugars, and nutrients to the brain’s neurons. In turn, the veins carry oxygen-free blood back to the heart, laden with waste pr

Dr. Jérôme Robert

oducts such as carbon dioxide, metabolic products, and, importantly for Alzheimer Disease, amyloid beta peptides.

 

 

How effectively blood flows to the brain is determined by a number of factors, including the width of the blood vessels, how thick the blood is, and the overall pressure of the blood’s flow to the brain. Too much or too little blood flowing to the brain can damage the brain’s tissues, according to Drs. Cheryl Wellington and Jerome Robert, who lead a team of researchers within the Canadian Consortium on Neurodegeneration in Aging.

 

Appreciating the need to protect the brain’s tissues, researchers have prioritized developing techniques to support proper blood flow. While their findings can offer new ways to treat brain disorders, including dementia, “a major barrier to progress is that there are few, if any, methods available to study the brain’s blood vessels outside of animal models,” Wellington explains.

 

Even though blood vessels are made up of several different types of cells, the majority of studies use a single type of cell grown in a test tube. Some try to combine two or more types of blood vessel cells. Considering that isolated cells are very different from an intact blood vessel, the other option is to study intact blood vessels in a mouse model. However, because mice do not always closely mimic what happens in the human body, the results may not help to develop effective treatments for dementia in human beings, says Wellington.

 

Marking a clear departure, Drs. Wellington and Robert have made considerable progress in developing three-dimensional blood vessels in test tubes, derived from individual cells from human beings. Specifically, by using tissue-engineering technology, the team has generated an experimental platform that can serve as the foundation for many types of studies on the blood vessels in the human brain.

 

Tissue engineering is a relatively new field of regenerative medicine, where functional, three- dimensional organs are grown in a test tube from individual cellular components. Engineered human blood vessels are already used in the clinic for bypass surgeries, and in patients that require lifelong dialysis. What’s exciting is that the team has created the first tissue engineered model of a cerebral blood vessel, namely, a blood vessel from the brain. They accomplished this by figuring out a way to engineer vessels that are surrounded by astrocytes, which are a special type of brain cell that naturally surrounds the brain’s blood vessels.

 

Their human-based platform – which allows for non-invasive and mechanistic experimentation – can bridge results of in vitro, animal model, and clinical studies.

 

In Wellington’s words,

 

“The significance of our work is to deliver a platform to help investigate blood and brain-derived compounds involved in neurodegenerative disease, as well as for drug discovery and development. We will, in a close future, be able to modify each parameter of the vessel – such as cell type, matrix, or flow – independently of other vascular constituents to better understand their role in the development and pathology of the disease. Our novel human-based model therefore offers considerable potential for sustained innovation in defining how vascular risk factors affect brain function.”