Effect of Microgravity on Drug Responses Using Engineered Heart Tissues
微重力对工程心脏组织药物反应的影响
基本信息
- 批准号:10670018
- 负责人:
- 金额:$ 19.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-22 至 2023-01-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAffectAfrican American populationAnimal ModelAnimalsArchitectureBiologicalBiologyCardiac MyocytesCardiomyopathiesCell CommunicationCell Culture TechniquesCell physiologyCellsClinicalDiseaseDrug ScreeningElectrophysiology (science)EnvironmentExposure toExtracellular MatrixForce of GravityHeartHeart failureHispanic AmericansHumanLaboratoriesMammalian CellMicrogravityModelingMolecularMyocardiumNormal CellOrganPatientsPatternPharmaceutical PreparationsPhasePhenotypePhysiologicalPhysiologyPlanet EarthRaceResearchSamplingSomatic CellTherapeuticTimeTissue EngineeringTissue MicroarrayTissuesTranslatingblastomere structurecardiac tissue engineeringcardiogenesiscaucasian Americancell typedisease phenotypedrug candidateethnic diversityextracellularheart functionhuman diseasein vitro Modelinduced pluripotent stem cellinduced pluripotent stem cell derived cardiomyocytesinsightinterestischemic cardiomyopathyracial diversityresponsescaffoldspace travelspatiotemporalthree dimensional structuretooltwo-dimensional
项目摘要
PROJECT SUMMARY
Tissue engineered organs or functional tissue-like ensembles contribute significantly to our understanding of
cellular niches that allow cells to migrate, develop and mature in three dimensions (3-D). Conventional two-
dimensional (2-D) mammalian cell culture does not represent the physiological environments that form the
basis for normal cell function. A 3-D environment promotes isotropic cell-cell communications, provides
extracellular guidance from structural matrix scaffolding, and allows spatiotemporal remodelling. Our specific
interest is in investigating the effects of microgravity on heart function with the use of Engineered Heart
Tissues (EHTs). Since these tissue engineering platforms support multicellular architecture from a ‘bottom-
up’ approach, it is critical to understand the mechanisms of heart development from a primordial state.
Although animal models are used widely to investigate biological responses to therapeutics, inherent
differences between human and animal biology combined with the unlikelihood of animals developing a
human disease limit the ability to validate research findings. Human induced pluripotent stem cells (hiPSCs)
have emerged as an indispensable tool to drive cells from an embryonic state to any somatic cell type. Our
laboratory’s focus and expertise in generating hiPSC-derived cardiomyocytes (hiPSC-CMs) and modelling of
cardiomyopathies has yielded deeper insight into several rare and common causes of heart failure. To
maintain a tissue-specific microenvironment, dissociated cells must be cultured in a physiologically relevant
3-D extracellular matrix (ECM). In the first phase (UG3), we will generate hiPSC-CMs from healthy patients
belonging to diverse racial groups (Caucasians, Hispanics, and African Americans). The hiPSC-CMs will be
used to fabricate our well-characterized EHT platforms, to understand cellular mechanisms that affect cardiac
function both under microgravity and earth’s gravity. Alterations in cardiac function due to weakened heart
muscles in the samples exposed to microgravity will be matched with molecular and electrophysiological
disease patterns observed in ischemic cardiomyopathy. In the second phase (UH3), the well-characterized
microgravity-induced disease phenotype will be translated on Heart Tissue Arrays (HTA) to screen for
potential drug candidates in a high-throughput manner. The proposed study will for the first time reveal key
functional and molecular differences that drive phenotypic changes in heart tissues on EHT assemblies under
influence of microgravity.
项目总结
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Wafer-Scale Patterning of Protein Templates for Hydrogel Fabrication.
- DOI:10.3390/mi12111386
- 发表时间:2021-11-12
- 期刊:
- 影响因子:3.4
- 作者:Kim AA;Castillo EA;Lane KV;Torres GV;Chirikian O;Wilson RE;Lance SA;Pardon G;Pruitt BL
- 通讯作者:Pruitt BL
Human Induced Pluripotent Stem Cells as a Screening Platform for Drug-Induced Vascular Toxicity.
- DOI:10.3389/fphar.2021.613837
- 发表时间:2021
- 期刊:
- 影响因子:5.6
- 作者:Tu C;Cunningham NJ;Zhang M;Wu JC
- 通讯作者:Wu JC
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Beth L Pruitt其他文献
Beth L Pruitt的其他文献
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{{ truncateString('Beth L Pruitt', 18)}}的其他基金
Predoctoral Training Program in Quantitative Mechanobiology
定量力学生物学博士前培训项目
- 批准号:
10439646 - 财政年份:2021
- 资助金额:
$ 19.66万 - 项目类别:
Predoctoral Training Program in Quantitative Mechanobiology
定量力学生物学博士前培训项目
- 批准号:
10626763 - 财政年份:2021
- 资助金额:
$ 19.66万 - 项目类别:
Predoctoral Training Program in Quantitative Mechanobiology
定量力学生物学博士前培训项目
- 批准号:
10207240 - 财政年份:2021
- 资助金额:
$ 19.66万 - 项目类别:
Effect of Microgravity on Drug Responses Using Engineered Heart Tissues
微重力对工程心脏组织药物反应的影响
- 批准号:
10173394 - 财政年份:2018
- 资助金额:
$ 19.66万 - 项目类别:
Effect of Microgravity on Drug Responses Using Engineered Heart Tissues
微重力对工程心脏组织药物反应的影响
- 批准号:
10239266 - 财政年份:2018
- 资助金额:
$ 19.66万 - 项目类别:
Validating engineered hiPSC-derived cardiomyocytes as model cells
验证工程化 hiPSC 衍生心肌细胞作为模型细胞
- 批准号:
9678119 - 财政年份:2016
- 资助金额:
$ 19.66万 - 项目类别:
Validating engineered hiPSC-derived cardiomyocytes as model cells
验证工程化 hiPSC 衍生心肌细胞作为模型细胞
- 批准号:
9030330 - 财政年份:2016
- 资助金额:
$ 19.66万 - 项目类别:
Force Clamp Systems for Evaluation of Mechanotransduction
用于评估机械传导的力夹系统
- 批准号:
7630592 - 财政年份:2007
- 资助金额:
$ 19.66万 - 项目类别:
Force Clamp Systems for Evaluation of Mechanotransduction
用于评估机械传导的力夹系统
- 批准号:
8147944 - 财政年份:2007
- 资助金额:
$ 19.66万 - 项目类别:
Force Clamp Systems for Evaluation of Mechanotransduction
用于评估机械传导的力夹系统
- 批准号:
7465346 - 财政年份:2007
- 资助金额:
$ 19.66万 - 项目类别:
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