A HUMAN IPSC-BASED 3D MICROPHYSIOLOGICAL SYSTEM FOR MODELING CARDIAC DYSFUNCTION IN MICROGRAVITY

基于 IPSC 的人体 3D 微生理系统，用于模拟微重力下的心脏功能障碍

• 批准号: 10175489
• 负责人: Deok-Ho Kim
• 金额: $ 31.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-24 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10175489
• 关键词: HUMAN; IPSC; BASED; 3D; MICROPHYSIOLOGICAL

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 magnetometer-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

项目成果

Conductive Silk-Polypyrrole Composite Scaffolds with Bioinspired Nanotopographic Cues for Cardiac Tissue Engineering.

• DOI: 10.1039/c8tb01116h
• 发表时间: 2018-11
• 期刊: Journal of materials chemistry. B
• 作者: Jonathan H. Tsui;Nicholas Ostrovsky-Snider;D. Yama;Jordan D. Donohue;J. Choi;Rakchanok Chavanachat

High-Throughput Contractility Assay for Human Stem Cell-Derived Cardiomyocytes.

人类干细胞来源的心肌细胞的高通量收缩性测定。

• DOI: 10.1161/circresaha.119.314844
• 发表时间: 2019
• 期刊: Circulation research
• 影响因子: 20.1
• 作者: Miklas,JasonW;Salick,MaxR;Kim,Deok-Ho
• 通讯作者: Kim,Deok-Ho