Engineered tools to study endocrine dysfunction of pancreas.

Abstract

Pancreas, a vital organ with intricate endocrine and exocrine functions, is central to the regulation of the body's glucose levels and digestive processes. Disruptions in its endocrine functions, primarily regulated by islets of Langerhans, can lead to debilitating diseases such as diabetes mellitus. Murine models of pancreatic dysfunction have contributed significantly to the understanding of insulitis, islet-relevant immunological responses, and the optimization of cell therapies. However, genetic differences between mice and humans have severely limited their clinical translational relevance. Recent advancements in tissue engineering and microfabrication have ushered in a new era of in vitro models that offer a promising solution. This paper reviews the state-of-the-art engineered tools designed to study endocrine dysfunction of the pancreas. Islet on a chip devices that allow precise control of various culture conditions and noninvasive readouts of functional outcomes have led to the generation of physiomimetic niches for primary and stem cell derived islets. Live pancreatic slices are a new experimental tool that could more comprehensively recapitulate the complex cellular interplay between the endocrine and exocrine parts of the pancreas. Although a powerful tool, live pancreatic slices require more complex control over their culture parameters such as local oxygenation and continuous removal of digestive enzymes and cellular waste products for maintaining experimental functionality over long term. The combination of islet-immune and slice on chip strategies can guide the path toward the next generation of pancreatic tissue modeling for better understanding and treatment of endocrine pancreatic dysfunctions.