TY - JOUR
KW - Animals
KW - Cell Culture Techniques
KW - Drug Evaluation
KW - Hypoglycemic Agents
KW - Islets of Langerhans
KW - Islets of Langerhans Transplantation
KW - Lab-On-A-Chip Devices
KW - Male
KW - Models, Biological
KW - Rats
KW - Rats, Sprague-Dawley
KW - Spheroids, Cellular
AU - Yesl Jun
AU - JaeSeo Lee
AU - Seongkyun Choi
AU - Ji Hun Yang
AU - Maike Sander
AU - Seok Chung
AU - Sang-Hoon Lee
AB - Native 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.
BT - Science Advances
DA - 2019-11
DO - 10.1126/sciadv.aax4520
IS - 11
LA - eng
N2 - Native 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.
PY - 2019
EP - eaax4520
T2 - Science Advances
TI - In vivo-mimicking microfluidic perfusion culture of pancreatic islet spheroids
VL - 5
SN - 2375-2548
ER -