Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model.
Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model.
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DOI：
10.1038/s41598-017-14815-w
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发表时间：
2017-11-06
影响因子：
4.6
通讯作者：
Andersson TB
中科院分区：
文献类型：
--
作者：
Bauer S;Wennberg Huldt C;Kanebratt KP;Durieux I;Gunne D;Andersson S;Ewart L;Haynes WG;Maschmeyer I;Winter A;Ämmälä C;Marx U;Andersson TB
研究疾病和药物治疗效果的人类体外生理模型迫切需要作为识别新药物靶点和疗法的更相关工具。我们建立了一个人体微流控双器官芯片模型，用于研究基于胰岛素和葡萄糖调节的胰岛-肝脏串扰。我们已经建立了一个强大的人胰岛微组织和肝球体的共培养，在无胰岛素培养基中维持功能反应长达15天。功能性偶联，表现为胰岛素释放的胰岛微组织在葡萄糖耐量试验中施加的葡萄糖负荷在不同的日子，促进葡萄糖摄取的肝球体。共培养维持餐后血糖浓度在循环中，而葡萄糖水平保持升高，在两个单一的文化。因此，分泌到循环中的胰岛素刺激了肝脏球状体对葡萄糖的摄取，而后者在没有胰岛素的情况下不能有效地消耗葡萄糖。随着葡萄糖浓度下降，胰岛素分泌减少，表明肝脏和分泌胰岛素的胰岛微组织之间存在功能反馈回路。最后，实验室间验证验证了耐用性和重现性。使用诱导葡萄糖调节受损的工具进一步开发该模型应提供模拟人2型糖尿病的独特体外系统。
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.
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DOI：
10.1016/j.ejpb.2015.03.002
发表时间：
2015-09
期刊：
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
影响因子：
--
作者：
Maschmeyer I;Hasenberg T;Jaenicke A;Lindner M;Lorenz AK;Zech J;Garbe LA;Sonntag F;Hayden P;Ayehunie S;Lauster R;Marx U;Materne EM
通讯作者：
Materne EM
在药物发现的边界，片上的器官。
DOI：
10.1038/nrd4539
发表时间：
2015-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Esch EW;Bahinski A;Huh D
通讯作者：
Huh D
DOI：
10.14573/altex.1603161
发表时间：
2016
期刊：
ALTEX
影响因子：
--
作者：
Marx U;Andersson TB;Bahinski A;Beilmann M;Beken S;Cassee FR;Cirit M;Daneshian M;Fitzpatrick S;Frey O;Gaertner C;Giese C;Griffith L;Hartung T;Heringa MB;Hoeng J;de Jong WH;Kojima H;Kuehnl J;Leist M;Luch A;Maschmeyer I;Sakharov D;Sips AJ;Steger-Hartmann T;Tagle DA;Tonevitsky A;Tralau T;Tsyb S;van de Stolpe A;Vandebriel R;Vulto P;Wang J;Wiest J;Rodenburg M;Roth A
通讯作者：
Roth A
影响因子：
3.8
作者：
Gunness, Patrina;Mueller, Daniel;Noor, Fozia
通讯作者：
Noor, Fozia
DOI：
10.1126/science.1188302
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Huh D;Matthews BD;Mammoto A;Montoya-Zavala M;Hsin HY;Ingber DE
通讯作者：
Ingber DE