Controlled aggregation of primary human pancreatic islet cells leads to glucose-responsive pseudoislets comparable to native islets

Journal of Cellular and Molecular Medicine
Janneke HilderinkAart A van Apeldoorn

Abstract

Clinical islet transplantation is a promising treatment for patients with type 1 diabetes. However, pancreatic islets vary in size and shape affecting their survival and function after transplantation because of mass transport limitations. To reduce diffusion restrictions and improve islet cell survival, the generation of islets with optimal dimensions by dispersion followed by reassembly of islet cells, can help limit the length of diffusion pathways. This study describes a microwell platform that supports the controlled and reproducible production of three-dimensional pancreatic cell clusters of human donor islets. We observed that primary human islet cell aggregates with a diameter of 100-150 μm consisting of about 1000 cells best resembled intact pancreatic islets as they showed low apoptotic cell death (<2%), comparable glucose-responsiveness and increasing PDX1, MAFA and INSULIN gene expression with increasing aggregate size. The re-associated human islet cells showed an a-typical core shell configuration with beta cells predominantly on the outside unlike human islets, which became more randomized after implantation similar to native human islets. After transplantation of these islet cell aggregates under the kidney caps...Continue Reading

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Methods Mentioned

BETA
chips
scanning electron microscopy
fluorescence microscopy
confocal microscopy
ELISA
PCR
chip
enzymatic dissociation

Software Mentioned

ImageJ

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