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Multiple-Condition Analysis in a Retrievable Subcutaneous Animal Model for Drug Screening on Full Pancreatic Tissue Digest.

Research paper by Tim W G M TWGM Spitters, Parker L PL Andersen, Chloé C Martel, Patrick P Vermette

Indexed on: 15 Aug '18Published on: 15 Aug '18Published in: Assay and drug development technologies



Abstract

The lack of understanding on how to treat pancreas-related diseases and develop new therapeutics is partly due to the unavailability of appropriate models. In vitro models fail to provide a physiological environment. Testing new drug targets in these models can give rise to bias and misleading results. Therefore, we developed an in vivo model for drug testing on full pancreatic digests, which maintains the interactions between endo- and exocrine tissues and allows retrieving the samples for further analyses. The use of full pancreatic digest eliminates the need to isolate islets, reducing time and cost. In this model, four different conditions can be implanted subcutaneously within the same animal. Each condition consists of full pancreatic tissue digests embedded in alginate beads. All alginate beads in one animal contained full pancreatic digest of the same donor and, after 5-day implantation, were retrieved for analysis focusing on survival, function, and/or organization. Proof-of-principle of the platform was evidenced by showing the effect of hyaluronic acid and vascular endothelial growth factor on the overall function of the full pancreatic digest and on endothelial cells in the pancreatic digest, respectively. Retrieval from identical animals allows direct comparison between conditions. Metabolism (MTT) quantification, dithizone staining, and glucose-stimulated insulin secretion assessment allow to discriminate, using a minimal number of animals, between treatments and validate the system. Because of its simplicity, the model is highly adaptable to specific needs of the user.