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Robust Fluidic Platforms for Organotypic Culture and Serial Assessment of Human and Rodent Pancreatic Slices
Dissertation

Robust Fluidic Platforms for Organotypic Culture and Serial Assessment of Human and Rodent Pancreatic Slices

Charles Garcia Alver
Doctor of Philosophy (PhD), University of Miami
2024-04

Abstract

Pancreatic slice Perfusion Organs on chips Ex-vivo cultures Microphysiological system Diabetes

            Enzymatically isolated pancreatic islets are the most commonly used ex vivo testbeds for diabetes research. Recently, precision-cut living slices of human pancreas are emerging as an exciting alternative because they maintain the complex architecture of the endocrine and exocrine tissues, and they do not suffer from the mechanical and chemical stress of enzymatic isolation. We report a fluidic pancreatic SliceChip platform with dynamic environmental controls that generates a warm, oxygenated, and bubble-free fluidic pathway across singular immobilized slices with continuous delivery of fresh media and the ability to perform repeat serial perfusion assessments. Maintenance of the physiological glucose-dependent insulin secretion profile across repeat perfusion assessments of individual pancreatic slices kept under physiological oxygen levels demonstrated the culture capacity of our platform. Our slice on a chip platform has the potential to expand the useability of human pancreatic slices for diabetes pathogenesis and the development of new therapeutic approaches while also enabling organotypic culture and assessment of other tissue slices, such as brain and patient tumors. Additionally, we lay out the basis for modification of other organs on chip devices for the inclusion of pancreatic slices as well as detailing potential clinical uses of the device.

 

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Embargoed Access, Embargo ends: 2026-04-22

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