Paoli Roberto, Samitier Josep
Nanobioengineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), Barcelona 08028, Spain.
Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid 28029, Spain.
Micromachines (Basel). 2016 Jul 20;7(7):126. doi: 10.3390/mi7070126.
Pharmaceutical drug screening and research into diseases call for significant improvement in the effectiveness of current in vitro models. Better models would reduce the likelihood of costly failures at later drug development stages, while limiting or possibly even avoiding the use of animal models. In this regard, promising advances have recently been made by the so-called "organ-on-chip" (OOC) technology. By combining cell culture with microfluidics, biomedical researchers have started to develop microengineered models of the functional units of human organs. With the capacity to mimic physiological microenvironments and vascular perfusion, OOC devices allow the reproduction of tissue- and organ-level functions. When considering drug testing, nephrotoxicity is a major cause of attrition during pre-clinical, clinical, and post-approval stages. Renal toxicity accounts for 19% of total dropouts during phase III drug evaluation-more than half the drugs abandoned because of safety concerns. Mimicking the functional unit of the kidney, namely the nephron, is therefore a crucial objective. Here we provide an extensive review of the studies focused on the development of a nephron-on-chip device.
药物筛选和疾病研究要求大幅提高当前体外模型的有效性。更好的模型将降低药物开发后期出现代价高昂的失败的可能性,同时限制甚至可能避免使用动物模型。在这方面,所谓的“芯片器官”(OOC)技术最近取得了有前景的进展。通过将细胞培养与微流体技术相结合,生物医学研究人员已开始开发人体器官功能单元的微工程模型。由于能够模拟生理微环境和血管灌注,OOC装置可实现组织和器官水平功能的再现。在考虑药物测试时,肾毒性是临床前、临床和批准后阶段药物淘汰的主要原因。在III期药物评估期间,肾毒性占总淘汰率的19%——超过因安全问题而被放弃药物的一半。因此,模拟肾脏的功能单元,即肾单位,是一个关键目标。在此,我们对专注于肾单位芯片装置开发的研究进行了全面综述。