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 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 机制和对伤害的反应，以及测试修复机制，所有这些都可以大大增强 治疗发现和评估。我们已经成功地描绘了新的分子驱动因素 疾病过程和药物所致的肾毒性。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对安全性的识别 和有效的治疗方法。 MPS疾病模型生成的数据集将提交给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、单元生长 条件和参数、IPSC分化条件、细胞特性(转录数据、批量和 单细胞RNA测序、基因分型、形态、细胞因子的产生/反应)，以及压力和 对小分子制剂的治疗反应。 我们相信，由组织芯片产生的可公开获取的数据将有助于MPS的接受 学术和工业环境中的技术，特别是当数据可以与 临床前和临床数据库。这项建议将允许提交来自MPS模型的现有数据 在成人和儿童中都发生的疾病状态，目前在MPS-DB中没有描述。 此外，我们将开发协议和模板来将数据提交合并到我们的实验中 确保及时提交未来数据的工作流程。

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.