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A Human iPSC-based 3D Microphysiological System for Modeling Cardiac Dysfunction in Microgravity

基于人体 iPSC 的 3D 微生理系统，用于模拟微重力下的心脏功能障碍

基本信息

批准号：
10460801
负责人：
Deok-Ho Kim
金额：
$ 5.79万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-24 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10460801
关键词：
3-Dimensional Address Adult Affect Aging Attenuated Biological Models Cardiac Cardiac Myocytes Cardiomyopathies Cardiovascular system Caring Cell Culture Techniques Cells Chronic Collection Cultured Cells Data Detection Development Disease Progression Drug Compounding Engineering Environment Exposure to Extracellular Matrix Force of Gravity Functional disorder Future Generations Genes Glean Heart Heart Diseases Human Human Engineering Human body In Situ In Vitro International Intervention Knowledge Lead Long-Term Effects Magnetism Measurement Mechanical Stimulation Mechanics Microgravity Mission Modeling Molecular Molecular Analysis Monitor Myocardial Myocardial dysfunction Myocardium Outcomes Research Patients Performance Pharmacologic Substance Phase Phenotype Physiological Planet Earth Planet Mars Process Regimen Role Signal Pathway Source Space Flight State of Zero Gravity Structure System Technology Testing Therapeutic Therapeutic Intervention Time Tissue Engineering Tissues Work base cardiac tissue engineering cardioprotection combat conditioning design differential expression experimental study heart function human model human tissue improved induced pluripotent stem cell instrumentation microphysiology system motion sensor novel novel therapeutic intervention prevent response scaffold sensor space station structural genomics transcriptomics

项目摘要

PROJECT SUMMARY Spaceflight has been shown to have a negative impact on the heart and the cardiovascular system. As we plan for exploration class missions that will see humans spend longer periods of time in space, such as in a manned missions to Mars, the potential impact of spaceflight on the heart and cardiovascular system will likely be increased. Additionally, the effects of spaceflight on the human body appear to mimic an accelerated aging process. Given that heart disease is the number one killer of all adults in the U.S., an understanding of the cardiogenic effects of microgravity may have implications for helping to treat millions of heart disease patients on Earth. Unfortunately, much is still unknown regarding the effect of spaceflight on the cardiovascular system and the heart in particular. To address this issue, we will develop a high-throughput microphysiological model of human cardiac muscle, derived from human induced pluripotent stem cells (hiPSCs), in order to study the effects of microgravity on cardiac tissue structure and physiological function. We will combine this cell source with a cardiac-specific decellularized extracellular matrix (dECM)-based electroconductive composite scaffold to promote the maturation of cultured cells. The technologies developed during this study will facilitate the generation of mature 3D engineered cardiac tissues that recapitulate the microarchitecture and function of human myocardium. The data collected using this platform aboard the International Space Station (ISS) will provide a better understanding of how prolonged microgravity affects the structure and function of the human heart. During the UG3 phase of this proposal, we will assess differences in cardiac function and physiological maturation between cells maintained in normal gravity and microgravity environments. Engineered heart tissues (EHTs) made from hiPSC-derived cardiomyocytes will be flown aboard the ISS for one month and be compared to identical ground controls. Real-time assessment of EHT contractility will be achieved via a novel magnetic coil-based motion sensor array, facilitating real-time and continuous assessment of function with minimal demands from the flight crew. Progressing to the UH3 phase, we will focus on the assessment of novel therapeutic strategies with which to attenuate microgravity-induced cardiomyopathy. We will assess both drug compounds and mechanical stimulation interventions and analyze each in isolation and in concert for their ability to improve cardiac function in space. The outcomes of this research could further improve our understanding of the progression of chronic heart diseases on Earth, and help drive the development of new therapeutic strategies for these debilitating conditions.

项目总结