02215nas a2200373   4500000000100000000000100001008004100002260001200043653002000055653001200075653002800087653001100115653002800126653002600154653002600180653002400206653002300230653001300253653001800266653002200284653002600306100001700332700001900349700001600368700001700384700001800401700002500419700001800444700001600462245007900478490000600557520126400563022001401827       2018                            d  c2018-0110a3D cell culture10aAnimals10aCell Culture Techniques10aHumans10aInsulin-Secreting Cells10aLab-On-A-Chip Devices10aRegenerative Medicine10aSpheroids, Cellular10aTissue engineering10aDiabetes10aorgan-on-chip10apancreatic islets10aRegenerative Medicine1 aSang Hun Lee1 aSoonGweon Hong1 aJihwan Song1 aByungrae Cho1 aEsther J. Han1 aSravani Kondapavulur1 aDongchoul Kim1 aLuke P. Lee00aMicrophysiological Analysis Platform of Pancreatic Islet β-Cell Spheroids0 v73 aThe hallmarks of diabetics are insufficient secretion of insulin and dysregulation of glucagon. It is critical to understand release mechanisms of insulin, glucagon, and other hormones from the islets of Langerhans. In spite of remarkable advancements in diabetes research and practice, robust and reproducible models that can measure pancreatic β-cell function are lacking. Here, a microphysiological analysis platform (MAP) that allows the uniform 3D spheroid formation of pancreatic β-cell islets, large-scale morphological phenotyping, and gene expression mapping of chronic glycemia and lipidemia development is reported. The MAP enables the scaffold-free formation of densely packed β-cell spheroids (i.e., multiple array of 110 bioreactors) surrounded with a perfusion flow network inspired by physiologically relevant microenvironment. The MAP permits dynamic perturbations on the β-cell spheroids and the precise controls of glycemia and lipidemia, which allow us to confirm that cellular apoptosis in the β-cell spheroid under hyperglycemia and hyperlipidemia is mostly dependent to a reactive oxygen species-induced caspase-mediated pathway. The β-cells' MAP might provide a potential new map in the pathophysiological mechanisms of β cells.  a2192-2659