Analysis of reproducibility and robustness of a human microfluidic four-cell liver acinus microphysiology system (LAMPS).
Analysis of reproducibility and robustness of a human microfluidic four-cell liver acinus microphysiology system (LAMPS).
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DOI：
10.1016/j.tox.2020.152651
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发表时间：
2021-01-30
期刊：
影响因子：
4.5
通讯作者：
Rusyn I
中科院分区：
文献类型：
--
作者：
Sakolish C;Reese CE;Luo YS;Valdiviezo A;Schurdak ME;Gough A;Taylor DL;Chiu WA;Vernetti LA;Rusyn I
对人类微流体四细胞肝腺泡微生理学系统 (LAMPS) 作为药物药代动力学和毒理学模型的重现性和稳健性进行了评估。该模型是使用原代人肝细胞或人诱导多能干细胞 (iPSC) 衍生的肝细胞以及内皮细胞、库普弗细胞和星状细胞的 3 种人类细胞系构建的。该模型在两个实验室进行了测试，并证明在培养 9 天的肝细胞基础功能、特非那定代谢以及托卡朋 (88 μM)、曲格列酮 (150 μM) 或咖啡因 (600 μM) 的影响方面具有可重复性。其他实验比较了 LAMPS 模型或接种原代肝细胞或 iPSC 肝细胞的 2D 培养物中白蛋白、尿素、乳酸脱氢酶 (LDH) 和肿瘤坏死因子 (TNF)α 的基础输出，以及药物代谢和毒性。进一步的实验研究了特非那定 (10 μM)、托卡朋 (88 μM)、曲伐沙星 (150 μM，含或不含 1 μg/mL 脂多糖)、曲格列酮 (28 μM)、罗格列酮 (0.8 μM)、吡格列酮 (3 μM) 和咖啡因 (600 μM) 的影响，为期 10 天。我们发现，与 2D 培养中的相同细胞相比，3D 培养中的原代人肝细胞和 iPSC 衍生的肝细胞在 10 天内都保持了良好的基础肝功能和特非那定代谢。在二维非重叠单层培养中，两种细胞类型在 48 小时后都失去了肝细胞表型。就药物作用而言，与 2D 培养物相比，两种细胞类型在 LAMPS 中都表现出可比且更与人类相关的作用。总体而言，这些研究表明，LAMPS 是一种稳健且可重复的体外肝脏模型，与原代人肝细胞或 iPSC 衍生肝细胞接种时的性能相当，并且比 2D 单层培养物更具生理和临床相关性。
A human microfluidic four-cell liver acinus microphysiology system (LAMPS), was evaluated for reproducibility and robustness as a model for drug pharmacokinetics and toxicology. The model was constructed using primary human hepatocytes or human induced pluripotent stem cell (iPSC)-derived hepatocytes and 3 human cell lines for the endothelial, Kupffer and stellate cells. The model was tested in two laboratories and demonstrated to be reproducible in terms of basal function of hepatocytes, Terfenadine metabolism, and effects of Tolcapone (88 μM), Troglitazone (150 μM), or caffeine (600 μM) over 9 days in culture. Additional experiments compared basal outputs of albumin, urea, lactate dehydrogenase (LDH) and tumor necrosis factor (TNF)α, as well as drug metabolism and toxicity in the LAMPS model, or 2D cultures seeded with either primary hepatocytes or iPSC-hepatocytes. Further experiments to study the effects of Terfenadine (10 μM), Tolcapone (88 μ), Trovafloxacin (150 μ with or without 1 μg/mL lipopolysaccharide), Troglitazone (28 μM), Rosiglitazone (0.8 μM), Pioglitazone (3 μM), and caffeine (600 μM) were carried out over 10 days. We found that both primary human hepatocytes and iPSC-derived hepatocytes in 3D culture maintained excellent basal liver function and Terfenadine metabolism over 10 days compared the same cells in 2D cultures. In 2D, non-overlay monolayer cultures, both cell types lost hepatocyte phenotypes after 48 hours. With respect to drug effects, both cell types demonstrated comparable and more human-relevant effects in LAMPS, as compared to 2D cultures. Overall, these studies show that LAMPS is a robust and reproducible in vitro liver model, comparable in performance when seeded with either primary human hepatocytes or iPSC-derived hepatocytes, and more physiologically and clinically relevant than 2D monolayer cultures.
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器官肝培养模型：应对毒性测试中当前的挑战。
影响因子：
5.9
作者：
LeCluyse EL;Witek RP;Andersen ME;Powers MJ
通讯作者：
Powers MJ
研究肝脏代谢对多器官人体芯片系统中脱靶心脏毒性的影响。
影响因子：
14
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Oleaga C;Riu A;Rothemund S;Lavado A;McAleer CW;Long CJ;Persaud K;Narasimhan NS;Tran M;Roles J;Carmona-Moran CA;Sasserath T;Elbrecht DH;Kumanchik L;Bridges LR;Martin C;Schnepper MT;Ekman G;Jackson M;Wang YI;Note R;Langer J;Teissier S;Hickman JJ
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Hickman JJ
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Godoy, Patricio;Hewitt, Nicola J.;Albrecht, Ute;Andersen, Melvin E.;Ansari, Nariman;Bhattacharya, Sudin;Bode, Johannes Georg;Bolleyn, Jennifer;Borner, Christoph;Boettger, Jan;Braeuning, Albert;Budinsky, Robert A.;Burkhardt, Britta;Cameron, Neil R.;Camussi, Giovanni;Cho, Chong-Su;Choi, Yun-Jaie;Rowlands, J. Craig;Dahmen, Uta;Damm, Georg;Dirsch, Olaf;Teresa Donato, Maria;Dong, Jian;Dooley, Steven;Drasdo, Dirk;Eakins, Rowena;Ferreira, Karine Sa;Fonsato, Valentina;Fraczek, Joanna;Gebhardt, Rolf;Gibson, Andrew;Glanemann, Matthias;Goldring, Chris E. P.;Jose Gomez-Lechon, Maria;Groothuis, Geny M. M.;Gustavsson, Lena;Guyot, Christelle;Hallifax, David;Hammad, Seddik;Hayward, Adam;Haeussinger, Dieter;Hellerbrand, Claus;Hewitt, Philip;Hoehme, Stefan;Holzhuetter, Hermann-Georg;Houston, J. Brian;Hrach, Jens;Ito, Kiyomi;Jaeschke, Hartmut;Keitel, Verena;Kelm, Jens M.;Park, B. Kevin;Kordes, Claus;Kullak-Ublick, Gerd A.;LeCluyse, Edward L.;Lu, Peng;Luebke-Wheeler, Jennifer;Lutz, Anna;Maltman, Daniel J.;Matz-Soja, Madlen;McMullen, Patrick;Merfort, Irmgard;Messner, Simon;Meyer, Christoph;Mwinyi, Jessica;Naisbitt, Dean J.;Nussler, Andreas K.;Olinga, Peter;Pampaloni, Francesco;Pi, Jingbo;Pluta, Linda;Przyborski, Stefan A.;Ramachandran, Anup;Rogiers, Vera;Rowe, Cliff;Schelcher, Celine;Schmich, Kathrin;Schwarz, Michael;Singh, Bijay;Stelzer, Ernst H. K.;Stieger, Bruno;Stoeber, Regina;Sugiyama, Yuichi;Tetta, Ciro;Thasler, Wolfgang E.;Vanhaecke, Tamara;Vinken, Mathieu;Weiss, Thomas S.;Widera, Agata;Woods, Courtney G.;Xu, Jinghai James;Yarborough, Kathy M.;Hengstler, Jan G.
通讯作者：
Hengstler, Jan G.
影响因子：
3.8
作者：
Monticello, Thomas M.;Jones, Thomas W.;Kadambi, Vivek J.
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Kadambi, Vivek J.
生物学启发的微生物生理系统，以提高患者的益处和动物福利。
DOI：
10.14573/altex.2001241
发表时间：
2020
期刊：
ALTEX
影响因子：
--
作者：
Marx U;Akabane T;Andersson TB;Baker E;Beilmann M;Beken S;Brendler-Schwaab S;Cirit M;David R;Dehne EM;Durieux I;Ewart L;Fitzpatrick SC;Frey O;Fuchs F;Griffith LG;Hamilton GA;Hartung T;Hoeng J;Hogberg H;Hughes DJ;Ingber DE;Iskandar A;Kanamori T;Kojima H;Kuehnl J;Leist M;Li B;Loskill P;Mendrick DL;Neumann T;Pallocca G;Rusyn I;Smirnova L;Steger-Hartmann T;Tagle DA;Tonevitsky A;Tsyb S;Trapecar M;Van de Water B;Van den Eijnden-van Raaij J;Vulto P;Watanabe K;Wolf A;Zhou X;Roth A
通讯作者：
Roth A