Dr. Kimberly Stroka, Associate Professor in the Fischell Department of Bioengineering at the University of Maryland College Park, engineers intricate cell model systems to study the blood-brain barrier (BBB) in the context of health and disease. The BBB is a dynamic neurovascular system that regulates the brain entry of various ions, nutrients, cells, and drugs. BBB dysfunction occurs in many neurological diseases and metastatic brain cancer. Up to 20% of people who have cancer will develop a metastatic brain tumor and an estimated 200,000 new cases of brain metastases are diagnosed in the U.S. every year.
Dr. Stroka and her lab generated a “blood-brain barrier on a chip”, a model system that mimics the BBB’s tissue microenvironment to further study brain metastasis. These brain tumor metastases indicate a severe progression of the disease and are more difficult to treat than a primary tumor. Dr. Stroka explains that brain metastasis “remains a devastating prognosis due to limited treatment options”, largely due to the lack of mechanistic understanding of how metastatic tumor cells invade across the highly selective brain barrier.
The BBB is mainly composed of endothelial cells, astrocytes, and pericytes that are in direct contact with brain tissue. These vascular endothelial cells are exposed to an array of mechanical forces in their microenvironment, including stiffness of the surrounding tissue and shear stress from blood flow. The Stroka lab focuses on understanding the unique interplay of the mechanical, biochemical, and biological cues in their BBB model system and how these cues may change in diseases such as metastatic brain cancer. Their research is unique because it allows them to assess the movement of tumor cells and their interaction with other cell types in a model that is applicable to the human body. Dr. Stroka describes how support from the Maryland Stem Cell Research Fund has “enabled us to make our blood-brain barrier model more physiologically relevant so that we can better understand the process of brain metastasis.”
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The “blood-brain barrier on a chip” is a microfluidic device composed of a small chip containing micro-channels that are similar in size to blood vessels. Additionally, hydrogel material is injected into this system to mimic the soft tissue surrounding the brain vessels along with induced pluripotent stem cell-derived brain microvascular endothelial cells. This engineered model system allows for the incorporation of mechanical parameters to assess the integrity and permeability of the endothelial cells in a context that is physiologically relevant to the BBB.
In addition to elucidating how tumor cells behave in this microenvironment, Dr. Stroka’s device is therapeutically applicable as it can shed light on the mechanism of drug transport across the BBB.
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11 сен 2024