Tissue Chip Data to the Microphysiology Systems Database (MPS-Db) Supplement to A Microphysiological System for Kidney Disease Modeling and Drug Efficacy Testing

摘要 为了满足对重现人类肾脏疾病的体外模型的迫切需求，我们开发了 一种体外肾脏芯片模型，概括了肾脏生理学的关键方面，可以评估 机制和对损伤的反应，并测试修复机制，所有这些都可以大大提高 治疗发现和评估。我们已经成功地描绘了新的分子驱动程序， 疾病过程和药物诱导的肾毒性。父应用程序的目标是推进我们的 “芯片上的肾脏”MPS，以模拟重要的人类肾脏疾病，并促进安全的 有效的治疗。 MPS疾病模型生成的数据集将提交至微生理学系统数据库 （MPS-Db）;这些数据将包括以下组件：MPS流程和芯片架构，细胞生长 条件和参数、iPSC分化条件、细胞特征（转录数据、体积和 单细胞RNA测序、基因分型、形态学、细胞因子产生/应答），以及应激和 对小分子试剂的治疗反应。 我们相信，从组织芯片产生的公开可访问的数据将有助于接受MPS 技术在学术和工业环境中，特别是当数据可以同时评估时， 临床前和临床数据库。该提案将使提交现有数据的MPS模型， 在成人和儿童中发生的疾病状态，目前在MPS-Db中没有代表。 此外，我们将开发协议和模板，将数据提交纳入我们的实验 工作流程，以确保及时提交未来数据。

ABSTRACT In response to the critical need for in vitro models that recapitulate human kidney diseases, we have developed an in vitro kidney chip model that recapitulates critical aspects of kidney physiology, can assess the mechanisms and response to injury, and test reparative mechanisms, all of which can substantially enhance therapeutic discovery and evaluation. We have demonstrated success in delineating novel molecular drivers of both disease processes and drug induced-nephrotoxicity. The goal of the parent application is to advance our ‘kidney on a chip’ MPS in order to model important human kidney diseases and promote identification of safe and effective treatments. Datasets generated from MPS disease models will be submitted to the Microphysiology Systems Database (MPS-Db); these data will include components including: MPS flow and chip architecture, cell growth conditions and parameters, iPSC differentiation conditions, cell characteristics (transcriptional data, bulk and single cell RNA sequencing, genotyping, morphology, cytokine production/response), and stress and therapeutic response to small molecule agents. We believe that publicly accessible data generated from tissue chips will facilitate acceptance of MPS technology in both academic and industrial settings, particularly when data can be evaluated in parallel with preclinical and clinical databases. This proposal will enable submission of existing data from MPS models of disease states that occur in both adults and children, and are not represented presently in the MPS-Db. Furthermore, we will develop protocols and templates to incorporate data submission into our experimental workflow to ensure timely submission of future data.