TY - JOUR
KW - Endocrine system and metabolic diseases
KW - Homeostasis
KW - Lab-on-a-chip
KW - Metabolic diseases
KW - Tissue engineering
AU - Sophie Bauer
AU - Charlotte Wennberg Huldt
AU - Kajsa P. Kanebratt
AU - Isabell Durieux
AU - Daniela Gunne
AU - Shalini Andersson
AU - Lorna Ewart
AU - William G. Haynes
AU - Ilka Maschmeyer
AU - Annika Winter
AU - Carina Ämmälä
AU - Uwe Marx
AU - Tommy B. Andersson
AB - Human in vitro physiological models studying disease and drug treatment effects are urgently needed as more relevant tools to identify new drug targets and therapies. We have developed a human microfluidic two-organ-chip model to study pancreatic islet–liver cross-talk based on insulin and glucose regulation. We have established a robust co-culture of human pancreatic islet microtissues and liver spheroids maintaining functional responses up to 15 days in an insulin-free medium. Functional coupling, demonstrated by insulin released from the islet microtissues in response to a glucose load applied in glucose tolerance tests on different days, promoted glucose uptake by the liver spheroids. Co-cultures maintained postprandial glucose concentrations in the circulation whereas glucose levels remained elevated in both single cultures. Thus, insulin secreted into the circulation stimulated glucose uptake by the liver spheroids, while the latter, in the absence of insulin, did not consume glucose as efficiently. As the glucose concentration fell, insulin secretion subsided, demonstrating a functional feedback loop between the liver and the insulin-secreting islet microtissues. Finally, inter-laboratory validation verified robustness and reproducibility. Further development of this model using tools inducing impaired glucose regulation should provide a unique in vitro system emulating human type 2 diabetes mellitus.
BT - Scientific Reports
DA - 2017-11-03
DO - 10.1038/s41598-017-14815-w
IS - 1
LA - en
N2 - Human in vitro physiological models studying disease and drug treatment effects are urgently needed as more relevant tools to identify new drug targets and therapies. We have developed a human microfluidic two-organ-chip model to study pancreatic islet–liver cross-talk based on insulin and glucose regulation. We have established a robust co-culture of human pancreatic islet microtissues and liver spheroids maintaining functional responses up to 15 days in an insulin-free medium. Functional coupling, demonstrated by insulin released from the islet microtissues in response to a glucose load applied in glucose tolerance tests on different days, promoted glucose uptake by the liver spheroids. Co-cultures maintained postprandial glucose concentrations in the circulation whereas glucose levels remained elevated in both single cultures. Thus, insulin secreted into the circulation stimulated glucose uptake by the liver spheroids, while the latter, in the absence of insulin, did not consume glucose as efficiently. As the glucose concentration fell, insulin secretion subsided, demonstrating a functional feedback loop between the liver and the insulin-secreting islet microtissues. Finally, inter-laboratory validation verified robustness and reproducibility. Further development of this model using tools inducing impaired glucose regulation should provide a unique in vitro system emulating human type 2 diabetes mellitus.
PY - 2017
EP - 14620
ST - Functional coupling of human pancreatic islets and liver spheroids on-a-chip
T2 - Scientific Reports
TI - Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model
UR - https://www.nature.com/articles/s41598-017-14815-w
VL - 7
Y2 - 2024-03-20
SN - 2045-2322
ER -