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
基本信息
- 批准号:9815578
- 负责人:
- 金额:$ 1.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-04-01 至 2020-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdipocytesAffectArrhythmiaArrhythmogenic Right Ventricular DysplasiaCardiacCardiac MyocytesCell-Cell AdhesionCellsCharacteristicsCoculture TechniquesDiseaseDisease ProgressionEngineeringEvaluationFatty acid glycerol estersFibrosisFunctional disorderGenetic DiseasesGenetic ModelsHeartHeart DiseasesHumanIn VitroIncidenceInfiltrationInterventionModelingMyocardial tissueMyocardiumMyofibroblastPatientsPhasePopulationPredispositionRiskSliceStructural defectStructureTestingTissuesUnited StatesWorkhuman stem cellsinduced pluripotent stem cellinsightparent grantscreeningsudden cardiac deathtool
项目摘要
PROJECT SUMMARY
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a powerful tool in
investigating cardiac disease by enabling us to model genetic cardiac conditions in vitro. Those models provide
unique insight into the pathophysiology of disease and allow for the screening and evaluation of potential
interventions. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disease affecting cell-cell
adhesion in cardiomyocytes. Arrhythmia associated with ARVC is a major cause of sudden cardiac death in
the United States, especially among young, low risk populations. The parent grant, “ARVD/C Dysfunction in
Human Stem Cell-Derived Cardiac Tissue” focuses on using iPSC-CMs derived from ARVC patients to
generate engineered heart slices (EHS) to study how structural defects promote arrhythmia in ARVC. While
that proposal focuses primarily on the early stages of the disease, when structural changes are not manifest on
a macroscopic scale, this project aims to create a late-stage model of ARVC, where fibrosis and fatty infiltrate
of myocardial tissue are prominent features. Thus, the Specific Aim of the project is to simulate the late-stage,
fibro-fatty disease condition of ARVC by addition of myofibroblasts and adipocytes to ARVC EHS. Phase 1 of
the project will be to create a fibrosis-like model of ARVC myocardium that displays characteristic conduction
slowing and increased incidence of reentrant arrhythmia by co-culturing hiPSC-CMs with myofibroblasts
(fibrosis-producing cells) in EHS. Phase 2 of the project will be to incorporate fatty infiltration into the fibrotic
ARVC EHS model by tri-culture of adipocytes (fat-producing cells) with hiPSC-CMs and myofibroblasts and to
test for further slowing of conduction and increased susceptibility to arrhythmia.
项目总结
人诱导多能干细胞来源的心肌细胞(hiPSC-CMS)为
通过使我们能够在体外模拟遗传性心脏疾病来研究心脏疾病。这些型号提供了
对疾病的病理生理学有独到的见解,并允许筛选和评估潜力
干预措施。致心律失常性右室心肌病(ARVC)是一种影响细胞的遗传性疾病
心肌细胞内的黏附。与ARVC相关的心律失常是#年心源性猝死的主要原因
在美国,特别是在年轻、低风险人群中。父母的资助,“ARVD/C功能障碍
《人类干细胞来源的心脏组织》侧重于使用来自ARVC患者的IPSC-CMS来治疗
生成工程化心脏切片(EHS)以研究结构缺陷如何促进ARVC中的心律失常。而当
该建议主要集中在疾病的早期阶段,此时结构变化在
作为一个宏观尺度,该项目旨在创建ARVC的晚期模型,在该模型中,纤维化和脂肪渗透
是心肌组织的显著特征。因此,该项目的具体目标是模拟后期,
通过在ARVC EHS中添加肌成纤维细胞和脂肪细胞,ARVC的纤维脂肪疾病状态。第1阶段:
该项目将创建一种类似纤维化的ARVC心肌模型,显示出特有的传导
HiPSC-CMS与肌成纤维细胞共培养减缓和增加折返性心律失常的发生率
(纤维化产生细胞)在EHS。该项目的第二阶段将是将脂肪渗透纳入纤维化
脂肪细胞(造脂细胞)与HiPSC-CMS和肌成纤维细胞三重培养建立ARVC EHS模型
测试传导是否进一步减慢并增加对心律失常的易感性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(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:
$ 1.7万 - 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:
$ 1.7万 - 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:
10250777 - 财政年份:2020
- 资助金额:
$ 1.7万 - 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:
$ 1.7万 - 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:
$ 1.7万 - 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:
$ 1.7万 - 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:
$ 1.7万 - 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:
$ 1.7万 - 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:
$ 1.7万 - 项目类别:
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