Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia
用于测试药物引起的心律失常的工程人体心脏切片
基本信息
- 批准号:10250777
- 负责人:
- 金额:$ 1.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-01 至 2023-03-31
- 项目状态:已结题
- 来源:
- 关键词:ArrhythmiaArrhythmogenic Right Ventricular DysplasiaBehaviorCD36 geneCardiacCardiac MyocytesCell LineCellsConfounding Factors (Epidemiology)DevelopmentDiseaseDisease modelDrug ModelingsEngineeringEntropyGeneticHeartHeart DiseasesHumanHuman EngineeringIn VitroMeasuresMetabolicMetabolic MarkerMethodsModelingNutrientPharmaceutical PreparationsPharmacologyProceduresProcessProtein IsoformsSarcomeresSliceSourceStructureTestingTimeTissuesTroponinWorkbasedrug testinghuman diseasehuman modelimprovedin vitro Modelinduced pluripotent stem cellinsightnovelparent grantresponsestem cellstherapeutic developmenttranscriptome sequencingtranscriptomics
项目摘要
The parent grant, “Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia”, aims to
develop a pharmacologic testing platform for in vitro prediction of drug-induced cardiac
arrhythmia using engineered heart slices (EHS) embedded with human induced pluripotent stem
cell-derived cardiomyocytes (hiPSC-CMs). Aim 1 focuses on improving methods of quantifying
and controlling the maturity of hiPSC-CMs, which is key to the implementation and interpretation
of these models. The work proposed here will supplement Aim 1 of the parent grant by expanding
beyond healthy wildtype hiPSC-CMs to understand maturity in hiPSCs harboring genetic cardiac
disorders, specifically arrhythmogenic right ventricular cardiomyopathy (ARVC). The first aim of
this work is to establish the maturation trajectory of diseased hiPSC-CMs in comparison to
wildtype cells. This will be accomplished by assessing, at several time points, structural features
(i.e. sarcomere organization, troponin isoform expression), CD36 positivity (marker of metabolic
maturity), and transcriptomic entropy scoring (a novel RNA-sequencing based method). The
second aim is to evaluate the effects of targeted metabolic maturation on diseased vs healthy
hiPSC-CMs. We will measure maturity in cells treated with standard differentiation procedures
and media against cells supplemented with a novel nutrient formula shown to boost maturity in
wildtype hiPSC-CMs. By providing insight into the maturational differences of healthy and disease
cells and potentially allowing us to account for that confounding variable, this work will facilitate
the creation of robust disease models for drug response testing and therapeutic development.
这项名为“用于检测药物引起的心律失常的人造人体心脏切片”的项目旨在
药物性心脏病体外预测药理实验平台的研制
人工诱导多能干细胞植入工程化心脏切片治疗心律失常
细胞来源的心肌细胞(HiPSC-CMS)。目标1侧重于改进量化方法
控制HiPSC-CMS的成熟度是实施和解释的关键
这些模型中的。这里提出的工作将通过扩展扩展来补充父赠款的目标1
超越健康野生型HiPSC-CMS了解携带遗传性心脏的HiPSC的成熟度
疾病,特别是致心律失常的右室心肌病(ARVC)。的第一个目标
本工作旨在建立病态HiPSC-CMS的成熟轨迹,并与
通配单元格。这将通过在几个时间点评估结构特征来实现
(即肌节组织、肌钙蛋白亚型表达)、CD36阳性(代谢标志物
成熟度),以及转录熵评分(一种基于RNA测序的新方法)。这个
第二个目的是评估靶向代谢成熟对疾病和健康的影响
HiPSC-CMS。我们将测量用标准分化程序处理的细胞的成熟度。
和添加了一种新的营养配方的细胞培养液,显示出可以促进
野生型HiPSC-CMS。通过提供对健康和疾病成熟差异的洞察
细胞,并潜在地允许我们解释这个令人困惑的变量,这项工作将有助于
为药物反应测试和治疗开发创建强大的疾病模型。
项目成果
期刊论文数量(0)
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{{ truncateString('LESLIE TUNG', 18)}}的其他基金
Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia
用于测试药物引起的心律失常的工程人体心脏切片
- 批准号:
10593346 - 财政年份:2020
- 资助金额:
$ 1.18万 - 项目类别:
Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia
用于测试药物引起的心律失常的工程人体心脏切片
- 批准号:
10593334 - 财政年份:2020
- 资助金额:
$ 1.18万 - 项目类别:
Mechanoelectrical Interactions Between Cardiac Myofibroblasts and Myocytes
心脏肌成纤维细胞和肌细胞之间的机电相互作用
- 批准号:
9204715 - 财政年份:2016
- 资助金额:
$ 1.18万 - 项目类别:
ARVD/C Dysfunction in Human Stem Cell-Derived Cardiac Tissue
人类干细胞来源的心脏组织中的 ARVD/C 功能障碍
- 批准号:
9815578 - 财政年份:2016
- 资助金额:
$ 1.18万 - 项目类别:
ARVD/C Dysfunction in Human Stem Cell-Derived Cardiac Tissue
人类干细胞来源的心脏组织中的 ARVD/C 功能障碍
- 批准号:
9106007 - 财政年份:2016
- 资助金额:
$ 1.18万 - 项目类别:
Mechanoelectrical Interactions Between Cardiac Myofibroblasts and Myocytes
心脏肌成纤维细胞和肌细胞之间的机电相互作用
- 批准号:
9028886 - 财政年份:2016
- 资助金额:
$ 1.18万 - 项目类别:
ARVD/C Dysfunction in Human Stem Cell-Derived Cardiac Tissue
人类干细胞来源的心脏组织中的 ARVD/C 功能障碍
- 批准号:
9251893 - 财政年份:2016
- 资助金额:
$ 1.18万 - 项目类别:
Functional Classification of Cardiomyocytes Derived from Stem Cells
干细胞来源的心肌细胞的功能分类
- 批准号:
8095482 - 财政年份:2011
- 资助金额:
$ 1.18万 - 项目类别:
Functional Classification of Cardiomyocytes Derived from Stem Cells
干细胞来源的心肌细胞的功能分类
- 批准号:
8259042 - 财政年份:2011
- 资助金额:
$ 1.18万 - 项目类别:
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