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

微生理学系统数据库 (MPS-Db) 的组织芯片数据补充用于肾脏疾病建模和药效测试的微生理学系统

• 批准号: 10435328
• 负责人: Jonathan Himmelfarb
• 金额: $ 7.58万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-25 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10435328
• 关键词: 3-Dimensional; APOL1 gene; ATAC-seq; Acute Renal Failure with Renal Papillary Necrosis; Administrative Supplement; Adult; Affect; Animal Model; Architecture; Autosomal Recessive Polycystic Kidney; Biological Markers; Biomedical Research; Blood Vessels; CRISPR/Cas technology; Cell Line; Cell model; Cells; Characteristics; Child; Chronic Kidney Failure; Clinical Trials; Data; Data Set; Database Management Systems; Development; Differentiation Antigens; Differentiation and Growth; Disease; Disease Progression; Disease model; Ensure; Epithelial Cells; Evaluation; Formulation; Functional disorder; Funding; Future; Genetic Transcription; Genotype; Goals; Growth; Health; Human; Human Resources; In Vitro; Industrialization; Internal Medicine; Intervention; Kidney; Kidney Diseases; Measurement; Microfluidics; Modeling; Modernization; Molecular; Morphology; Nephrology; Nephrons; Organ; Organoids; Parents; Pathogenesis; Pathway Analysis; Pathway interactions; Pharmaceutical Preparations; Pharmacology; Physiology; Polycystic Kidney Diseases; Preclinical Drug Development; Process; Production; Proteinuria; Protocols documentation; Public Health; Publishing; Quality of life; Randomized Clinical Trials; Renin-Angiotensin System; Serum; Shiga Toxin; Structure; System; Technology; Testing; Therapeutic; Time; Tissue Microarray; Toxicity Tests; Translating; biological adaptation to stress; cell growth; clinical database; comorbidity; cytokine; data standards; data submission; drug candidate; drug development; drug efficacy; effective therapy; efficacy testing; epigenomics; high throughput screening; human model; improved; in vitro Model; in vivo; induced pluripotent stem cell; inhibitor/antagonist; kidney cell; medical specialties; microphysiology system; morphometry; mortality; nephrotoxicity; novel; novel therapeutics; parent grant; pre-clinical; response; response to injury; shear stress; side effect; single-cell RNA sequencing; small molecule; success; thrombotic; transcriptome sequencing; transcriptomics; treatment response; two-dimensional; urinary

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.

抽象的 为了响应对概括人类肾脏疾病的体外模型的关键需求，我们已经开发了 一个概括肾脏生理学关键方面的体外肾脏芯片模型，可以评估 机制和对伤害的反应和测试修复机制，所有这些机制都可以大大增强 治疗发现和评估。我们在描述新的分子驱动器方面取得了成功 疾病过程和药物引起的肺毒性。父母申请的目标是促进我们的 为了对重要的人类肾脏疾病进行建模并促进安全的识别 和有效的治疗方法。 由MPS病模型产生的数据集将提交给微生物生理系统数据库 （MPS-DB）;这些数据将包括：MPS流量和芯片结构，细胞生长，包括： 条件和参数，IPSC分化条件，细胞特征（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）以及应力和 对小分子剂的治疗反应。 我们认为，从组织芯片产生的公共访问数据将有助于接受国会议员 在学术和工业环境中的技术，尤其是可以与数据并行评估的数据 临床前和临床数据库。该建议将使从MPS模型中提交现有数据 在成人和儿童中都发生的疾病状态，在MPS-DB中没有代表。 此外，我们将开发协议和模板以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。

项目成果

Targeting an anchored phosphatase-deacetylase unit restores renal ciliary homeostasis.

• DOI: 10.7554/elife.67828
• 发表时间: 2021-07-12
• 期刊: eLife
• 影响因子: 7.7
• 作者: Gopalan J;Omar MH;Roy A;Cruz NM;Falcone J;Jones KN;Forbush KA;Himmelfarb J;Freedman BS;Scott JD
• 通讯作者: Scott JD

COVID-19 Vasculopathy: Mounting Evidence for an Indirect Mechanism of Endothelial Injury.

• DOI: 10.1016/j.ajpath.2021.05.007
• 发表时间: 2021-08
• 期刊: The American journal of pathology
• 作者: Nicosia RF;Ligresti G;Caporarello N;Akilesh S;Ribatti D
• 通讯作者: Ribatti D

Producing Purer Podocytes.

产生更纯的足细胞。

• DOI: 10.1681/asn.2018101045
• 发表时间: 2019
• 期刊: Journal of the American Society of Nephrology : JASN
• 作者: Freedman,BenjaminS