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Mechanotransduction Regulates Endothelial Cell Behavior in an In Vitro Blood Brain Barrier Model

Thursday, August 22, 2019

2:00 PM-3:30 PM

BIOMED Special Seminar

Mechanotransduction Regulates Endothelial Cell Behavior in an In Vitro Blood Brain Barrier Model

Aylin Sendemir, PhD
Professor of Engineering
Department of Bioengineering
Ege University
Izmir, Turkey

There are several blood-brain barrier (BBB) models frequently used in drug development, screening, and targeting studies, but none of those are able to properly replicate the physiological permeabilities of this special barrier.

The aim of this study is the construction of a reliable in vitro BBB model mimicking physiological BBB characteristics, in terms of cellular organization and mechanobiology. Bacterial cellulose (BC) is chosen as a basement membrane. Because of BC’s nano-porous structure, the nutrient transfer is enabled, while cell migration is restricted. BC was produced both in sheet and vessel forms, for static and dynamic cultivation, respectively.

For the dynamic model, BBB bioreactor system was designed and constructed in order to simulate the physiological blood flow and shear stress in brain capillaries. Human brain microvascular endothelial cells (HBMECs) were seeded in luminal section and astrocytes and human brain microvascular pericytes (HBMPCs) were seeded in the abluminal section, and were cultivated together without changing compartments. Cell viability was observed by Live&Dead staining. Immunofluorescence (IF) staining was performed in order to observe specific markers of the cells, and scanning electron microscopy (SEM) was performed in order to observe morphology of the cells. Caffeine and sucrose permeabilites of the models were determined by HPLC analysis, and trans-endothelial electrical resistance (TEER) values were measured by epithelial volt/ohm meter. The expression levels of tight and adherence junction proteins of HBMECs were analyzed by quantitative polymerase chain reaction (qPCR).

This work has been supported by the Scientific and Technological Research Council of Turkey (TUBITAK) through Project no: 216M542.

Aylin Sendemir, PhD, graduated as a mechanical engineer from Bogazici University, Istanbul, Turkey (1994. She received her MSc degree from the Institute of Biomedical Engineering from Bogazici University (1997), and her PhD degree in Materials Science and Engineering from University of Illinois at Urbana-Champaign, USA.

Dr. Sendemir is an Associate Professor in the Department of Bioengineering at Ege University, Izmir, Turkey, and is currently the principal investigator of Ege Research Group of Biomaterials and 3D Biointerphases (EBioPhase). Her research interests include interactions of animal cells and biomaterials, tissue engineering, mechano-transduction, stem cells, cancer stem cells, and biocompatibility testing. She is particularly interested in the design and production of novel in vitro tissue engineered 3D personalized disease models for pharmaceutical screening and minimizing animal testing.

Dr. Sendemir is a member of the Editorial Boards of Tissue Engineering, and Challenges in Regenerative Medicine. She is among the founding members of the Turkish Biodesign Team (TBT), and has co-authored more than 25 scientific papers, 3 patents, and 5 book chapters.

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