Development of a Microfluidic Thyroid-on-a-Chip Model to Study Fluidic Effects on Cellular Behavior

Authors

• DM King
• MR Sapio
• D Maric
• AP Manalo
• A Ghetti
• MJ Iadarola
• AJ Mannes

Abstract

Thyroid disorders, including autoimmune disorders and cancer, are complex conditions with far-reaching effects. Many studies have attempted to further elucidate the development and progression of these conditions through the use of animal and cell culture models. However, newer modeling techniques such as organ-on-a-chip devices provide the potential for higher accuracy in modeling organ physiology as well as personalized modeling. We are developing a vascularized organ-on-a-chip model of the thyroid for use in studying thyroid autoimmune diseases and cancer. We have induced the formation of thyroid microvasculature by culturing primary human thyroid microvascular endothelial cells (HTMECs) on basement membrane extract. Furthermore, through a similar procedure, we have established a protocol for the formation of thyroid follicle-like organoids from immortalized human thyroid epithelial cells (huThyrECs). We intend next to explore the results of co-culturing the HTMECs and huThyrECs, in hopes of obtaining organoids interconnected by tubular networks. Our goal is to develop a microchannel device into which we can seed the HTMECs and huThyrECs in order to obtain a vascularized structure replete with thyroid follicles which reflects the native structure of the human thyroid. We will then evaluate the effects of flow on the behavior of the cells and characterize the architecture and microenvironment present in the chip. Following development and optimization of the chip, the device may prove valuable as a tool to model the diseased state of the thyroid under autoimmune or cancerous conditions.

Scientific Focus Area: ACI/IRS

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