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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：
Beth L Pruitt
金额：
$ 19.66万
依托单位：
STANFORD UNIVERSITY
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：
https://reporter.nih.gov/project-details/10670018
关键词：
3-Dimensional Affect African American population Animal Model Animals Architecture Biological Biology Cardiac Myocytes Cardiomyopathies Cell Communication Cell Culture Techniques Cell physiology Cells Clinical Disease Drug Screening Electrophysiology (science)Environment Exposure to Extracellular Matrix Force of Gravity Heart Heart failure Hispanic Americans Human Laboratories Mammalian Cell Microgravity Modeling Molecular Myocardium Normal Cell Organ Patients Pattern Pharmaceutical Preparations Phase Phenotype Physiological Physiology Planet Earth Race Research Sampling Somatic Cell Therapeutic Time Tissue Engineering Tissue Microarray Tissues Translating blastomere structure cardiac tissue engineering cardiogenesis caucasian American cell type disease phenotype drug candidate ethnic diversity extracellular heart function human disease in vitro Model induced pluripotent stem cell induced pluripotent stem cell derived cardiomyocytes insight interest ischemic cardiomyopathy racial diversity response scaffold space travel spatiotemporal three dimensional structure tool two-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：
Micromachines
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.