Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies.
Establishing quasi-steady state operations of microphysiological systems (MPS) using tissue-specific metabolic dependencies.
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DOI：
10.1038/s41598-018-25971-y
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发表时间：
2018-05-22
影响因子：
4.6
通讯作者：
Cirit M
中科院分区：
文献类型：
--
作者：
Maass C;Dallas M;LaBarge ME;Shockley M;Valdez J;Geishecker E;Stokes CL;Griffith LG;Cirit M
微生理系统（MPS）由组织结构、生物材料和培养基组成，旨在体外重现相关器官功能。MPS组件容纳在具有操作协议的流体硬件中，例如定期完全更换培养基。这种分批式操作提供了相关的营养物质并去除了废物，但也重置了细胞分泌的介质（例如细胞因子、激素），并可能限制药物（和代谢物）的暴露。虽然每种成分对组织功能都起着至关重要的作用，但MPS特定的营养需求尚未得到很好的表征，也未被用于在更生理相关的条件下操作MPS。通过实验定量了肠（永生化癌细胞）、肝（人原代肝细胞）和心脏（iPSC衍生的心肌细胞）MPS的MPS特异性营养需求。在肠道MPS的长期研究（10天）中，这些知识用于设计操作方案，以将葡萄糖和乳酸盐维持在所需水平。通过监测葡萄糖和乳酸盐以及MPS功能，对这种准稳态操作进行了实验验证。在一项理论研究中，通过计算模拟了集成多MPS平台（肠道、肝脏、心脏MPS）的营养需求，以确定长期准稳态操作。这种综合性的实验和计算方法表明，利用定量多尺度表征的MPS和MPS的具体信息，建立更多的生理相关的实验操作。
Microphysiological systems (MPS), consisting of tissue constructs, biomaterials, and culture media, aim to recapitulate relevant organ functions in vitro. MPS components are housed in fluidic hardware with operational protocols, such as periodic complete media replacement. Such batch-like operations provide relevant nutrients and remove waste products but also reset cell-secreted mediators (e.g. cytokines, hormones) and potentially limit exposure to drugs (and metabolites). While each component plays an essential role for tissue functionality, MPS-specific nutrient needs are not yet well-characterized nor utilized to operate MPSs at more physiologically-relevant conditions. MPS-specific nutrient needs for gut (immortalized cancer cells), liver (human primary hepatocytes) and cardiac (iPSC-derived cardiomyocytes) MPSs were experimentally quantified. In a long-term study of the gut MPS (10 days), this knowledge was used to design operational protocols to maintain glucose and lactate at desired levels. This quasi-steady state operation was experimentally validated by monitoring glucose and lactate as well as MPS functionality. In a theoretical study, nutrient needs of an integrated multi-MPS platform (gut, liver, cardiac MPSs) were computationally simulated to identify long-term quasi-steady state operations. This integrative experimental and computational approach demonstrates the utilization of quantitative multi-scale characterization of MPSs and incorporating MPS-specific information to establish more physiologically-relevant experimental operations.
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癌细胞对葡萄糖限制和双胍类药物敏感性的代谢决定因素。
影响因子：
64.8
作者：
Birsoy, Kivanc;Possemato, Richard;Lorbeer, Franziska K.;Bayraktar, Erol C.;Thiru, Prathapan;Yucel, Burcu;Wang, Tim;Chen, Walter W.;Clish, Clary B.;Sabatini, David M.
通讯作者：
Sabatini, David M.
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：
Doherty, Kimberly R.;Wappel, Robert L.;Bacus, Sarah
通讯作者：
Bacus, Sarah
影响因子：
4.6
作者：
Edington CD;Chen WLK;Geishecker E;Kassis T;Soenksen LR;Bhushan BM;Freake D;Kirschner J;Maass C;Tsamandouras N;Valdez J;Cook CD;Parent T;Snyder S;Yu J;Suter E;Shockley M;Velazquez J;Velazquez JJ;Stockdale L;Papps JP;Lee I;Vann N;Gamboa M;LaBarge ME;Zhong Z;Wang X;Boyer LA;Lauffenburger DA;Carrier RL;Communal C;Tannenbaum SR;Stokes CL;Hughes DJ;Rohatgi G;Trumper DL;Cirit M;Griffith LG
通讯作者：
Griffith LG
影响因子：
2.9
作者：
Meadows, Adam L.;Kong, Becky;Clark, Douglas S.
通讯作者：
Clark, Douglas S.