02028nas a2200361   4500000000100000000000100001008004100002260001200043653001200055653002800067653002000095653002400115653002500139653004100164653002600205653000900231653002300240653000900263653002500272653002400297100001300321700001500334700001900349700001600368700001700384700001500401700001800416245008300434300001300517490000600530520111600536022001401652       2019                            d  c2019-1110aAnimals10aCell Culture Techniques10aDrug Evaluation10aHypoglycemic Agents10aIslets of Langerhans10aIslets of Langerhans Transplantation10aLab-On-A-Chip Devices10aMale10aModels, Biological10aRats10aRats, Sprague-Dawley10aSpheroids, Cellular1 aYesl Jun1 aJaeSeo Lee1 aSeongkyun Choi1 aJi Hun Yang1 aMaike Sander1 aSeok Chung1 aSang-Hoon Lee00aIn vivo-mimicking microfluidic perfusion culture of pancreatic islet spheroids  aeaax45200 v53 aNative pancreatic islets interact with neighboring cells by establishing three-dimensional (3D) structures, and are surrounded by perfusion at an interstitial flow level. However, flow effects are generally ignored in islet culture models, although cell perfusion is known to improve the cell microenvironment and to mimic in vivo physiology better than static culture systems. Here, we have developed functional islet spheroids using a microfluidic chip that mimics interstitial flow conditions with reduced shear cell damage. Dynamic culture, compared to static culture, enhanced islet health and maintenance of islet endothelial cells, reconstituting the main component of islet extracellular matrix within spheroids. Optimized flow condition allowed localization of secreted soluble factors near spheroids, facilitating diffusion-mediated paracrine interactions within islets, and enabled long-term maintenance of islet morphology and function for a month. The proposed model can aid islet preconditioning before transplantation and has potential applications as an in vitro model for diabetic drug testing.  a2375-2548