Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs.
Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs.
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DOI：
10.1038/srep20030
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发表时间：
2016-02-03
影响因子：
4.6
通讯作者：
Hickman JJ
中科院分区：
文献类型：
--
作者：
Oleaga C;Bernabini C;Smith AS;Srinivasan B;Jackson M;McLamb W;Platt V;Bridges R;Cai Y;Santhanam N;Berry B;Najjar S;Akanda N;Guo X;Martin C;Ekman G;Esch MB;Langer J;Ouedraogo G;Cotovio J;Breton L;Shuler ML;Hickman JJ
我们报告了一个功能性人体模型，以评估在连续流动条件下，在无血清限定培养基中，利用无泵平台14天的4器官系统中的多器官毒性。平台的计算机模拟确定了可接受范围内的流速和所得剪切应力。系统的活力被证明了14天，以及心脏，肌肉，神经元和肝脏模块的功能活性。在48小时药物治疗方案后，评价了集成模块在7天时对5种具有已知副作用的药物的反应的药理学相关性。所有药物治疗的结果与已发表的人类和动物数据的毒性结果基本一致。所提出的表型培养模型表现出多器官毒性反应，代表了下一代体外系统，并构成了一个步骤，在体外“芯片上的人”测定全身毒性筛选。
We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems, and constitutes a step towards an in vitro “human-on-a-chip” assay for systemic toxicity screening.