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Jen (Niemczyk) Mantle

BS: Chemical Engineering, Villanova University

Contact Information:
Email username (at niemczyk
Office: 270 DBI
Phone: (302) 831-4410

Research Project:

Currently 5.2 million Americans are living with Alzheimer’s disease, and this figure is projected to increase to 7.1 million by 2025 [1]. Treatments are limited because systemically delivered drugs are restricted from crossing the blood-brain barrier (BBB) and reaching their target destination in the brain. The BBB is composed of brain microvascular endothelial cells (BMECs)that line cerebral capillaries and regulate the microenvironment of the brain. Compared to animal models, in vitro BBB models provide a more controllable, high throughput, and cost effective way to study the transport of therapeutics across the BBB. Current in vitro BBB models are limited by tissue availability and cell health in the case of human-derived models, and species differences and loss of brain-specific properties in the case of animal-derived models. For example, primary murine models typically achieve transendothelial electrical resistance (TEER) values around 200 Ω·cm2 [2] which is an order of magnitude lower than TEER values measured in the brain. Consequently, physiologically relevant in vitro BBB models derived from renewable human cells are needed to better mimic the in vivo environment and enhance the study of drug transport across the BBB.

Recently, a workflow was developed to differentiate human induced pluripotent stem cells (hiPSCs) into BMECs [3]. This research replicates and improves techniques to culture and differentiate hiPSCs into BMECs for use in an in vitro BBB model. We have been able to achieve physiologically relevant barrier properties, characterized by high TEER and by the expression and localization of BMEC-specific proteins. TEER values consistently exceed 1500 Ω·cm2 which is within the physiological range. This model will be used to investigate the biological transport mechanisms of therapeutics, including intravenous immunoglobulin (IVIG), a drug currently in clinical trials for the treatment of Alzheimer’s disease.

[1] “Latest Facts & Figures Report | Alzheimer's Association." Latest Facts & Figures Report | Alzheimer's Association. Web. 29 July 2013.

[2] Wuest, DM., et al. “Membrane configuration optimization for a murine in vitro blood—brain barrier model.” Journal of Neuroscience Methods 212, 311-221 (2013).

[3] Lippmann, ES., et al. “Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells.” Nature Biotechnology 30, 783–791 (2012).

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