A HUMAN IPSC-BASED 3D MICROPHYSIOLOGICAL SYSTEM FOR MODELING CARDIAC DYSFUNCTION IN MICROGRAVITY
A HUMAN IPSC-BASED 3D MICROPHYSIOLOGICAL SYSTEM FOR MODELING CARDIAC DYSFUNCTION IN MICROGRAVITY
批准号:
10175489
负责人:
Deok-Ho Kim
金额:
$31.35万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-24 至 2020-06-30
中文摘要
项目概要
太空飞行已被证明对心脏和心血管系统有负面影响。正如我们计划的那样
对于探索类任务,人类将在太空中度过更长的时间,例如载人飞船
火星任务中,太空飞行对心脏和心血管系统的潜在影响可能是
增加。此外,太空飞行对人体的影响似乎类似于加速衰老
过程。鉴于心脏病是美国所有成年人的头号杀手,了解
微重力的心源性影响可能有助于治疗数百万心脏病患者
在地球上。不幸的是,关于太空飞行对心血管系统的影响仍然未知
尤其是心脏。为了解决这个问题,我们将开发一个高通量的微生理模型
人类心肌,源自人类诱导多能干细胞 (hiPSC),以研究效果
微重力对心脏组织结构和生理功能的影响。我们将把这个细胞源与
基于心脏特异性脱细胞细胞外基质(dECM)的导电复合支架
促进培养细胞的成熟。本研究期间开发的技术将促进
生成成熟的 3D 工程心脏组织,再现心脏的微结构和功能
人类心肌。使用该平台在国际空间站 (ISS) 上收集的数据将
更好地了解长期微重力如何影响人类的结构和功能
心。在该提案的 UG3 阶段,我们将评估心脏功能和生理学的差异
在正常重力和微重力环境下维持细胞之间的成熟。工程心脏组织
由 hiPSC 衍生的心肌细胞制成的 (EHT) 将在国际空间站飞行一个月并进行比较
到相同的地面控制。 EHT 收缩性的实时评估将通过一种新颖的方法来实现
基于磁力计的运动传感器阵列,促进实时和连续的功能评估
对机组人员的最低要求。进入UH3阶段,我们将重点评估小说
减轻微重力诱发的心肌病的治疗策略。我们将评估这两种药物
化合物和机械刺激干预措施,并单独和一致地分析每种干预措施的能力
改善太空中的心脏功能。这项研究的结果可以进一步加深我们对
地球上慢性心脏病的进展,并有助于推动新治疗策略的开发
对于这些令人衰弱的情况。
英文摘要
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
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.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1039/c8tb01116h
发表时间:
2018-11
期刊:
Journal of materials chemistry. B
影响因子:
--
作者:
[Jonathan H. Tsui;Nicholas Ostrovsky-Snider;D. Yama;Jordan D. Donohue;J. Choi;Rakchanok Chavanachat;]
通讯作者:
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
High-throughput nanoIEA-based Assay for Screening Immune Cell-Vascular Interactions
-
批准号:10592897
-
项目类别:
-
资助金额:$21.17万
-
财政年份:2023
-
负责人:Deok-Ho Kim
-
依托单位:
Microphysiological Model of Human Cardiac Sympathetic Innervation
-
批准号:10502626
-
项目类别:
-
资助金额:$74.18万
-
财政年份:2022
-
负责人:Deok-Ho Kim
-
依托单位:
Microphysiological Model of Human Cardiac Sympathetic Innervation
-
批准号:10869757
-
项目类别:
-
资助金额:$7.42万
-
财政年份:2022
-
负责人:Deok-Ho Kim
-
依托单位:
Microphysiological Model of Human Cardiac Sympathetic Innervation
-
批准号:10861445
-
项目类别:
-
资助金额:$5.42万
-
财政年份:2022
-
负责人:Deok-Ho Kim
-
依托单位:
A Human iPSC-based 3D Microphysiological System for Modeling Cardiac Dysfunction in Microgravity
-
批准号:10632929
-
项目类别:
-
资助金额:$32.67万
-
财政年份:2022
-
负责人:Deok-Ho Kim
-
依托单位:
Microphysiological Model of Human Cardiac Sympathetic Innervation
-
批准号:10636892
-
项目类别:
-
资助金额:$71.56万
-
财政年份:2022
-
负责人:Deok-Ho Kim
-
依托单位:
Transcriptomic Entropy to Quantify Maturation of PSC-Derived Cardiomyocytes
-
批准号:10179233
-
项目类别:
-
资助金额:$56.98万
-
财政年份:2021
-
负责人:Deok-Ho Kim
-
依托单位:
Transcriptomic Entropy to Quantify Maturation of PSC-Derived Cardiomyocytes
-
批准号:10378025
-
项目类别:
-
资助金额:$56.98万
-
财政年份:2021
-
负责人:Deok-Ho Kim
-
依托单位:
Transcriptomic Entropy to Quantify Maturation of PSC-Derived Cardiomyocytes
-
批准号:10661492
-
项目类别:
-
资助金额:$56.98万
-
财政年份:2021
-
负责人:Deok-Ho Kim
-
依托单位:
DISEASE MODELING AND PHENOTYPIC DRUG SCREENING FOR DYSTROPHIC CARDIOMYOPATHY
-
批准号:10164856
-
项目类别:
-
资助金额:$53.17万
-
财政年份:2020
-
负责人:Deok-Ho Kim
-
依托单位:
DISEASE MODELING AND PHENOTYPIC DRUG SCREENING FOR DYSTROPHIC CARDIOMYOPATHY
-
批准号:10116566
-
项目类别:
-
资助金额:$52.09万
-
财政年份:2020
-
负责人:Deok-Ho Kim
-
依托单位:
DISEASE MODELING AND PHENOTYPIC DRUG SCREENING FOR DYSTROPHIC CARDIOMYOPATHY
-
批准号:10396049
-
项目类别:
-
资助金额:$53.17万
-
财政年份:2020
-
负责人:Deok-Ho Kim
-
依托单位:
A Human iPSC-based 3D Microphysiological System for Modeling Cardiac Dysfunction in Microgravity
-
批准号:10434471
-
项目类别:
-
资助金额:$8.04万
-
财政年份:2018
-
负责人:Deok-Ho Kim
-
依托单位:
A Human iPSC-based 3D Microphysiological System for Modeling Cardiac Dysfunction in Microgravity
-
批准号:10268228
-
项目类别:
-
资助金额:$75.77万
-
财政年份:2018
-
负责人:Deok-Ho Kim
-
依托单位:
A Human iPSC-based 3D Microphysiological System for Modeling Cardiac Dysfunction in Microgravity
-
批准号:9791191
-
项目类别:
-
资助金额:$42.15万
-
财政年份:2018
-
负责人:Deok-Ho Kim
-
依托单位:
A Human iPSC-based 3D Microphysiological System for Modeling Cardiac Dysfunction in Microgravity
-
批准号:10460801
-
项目类别:
-
资助金额:$5.79万
-
财政年份:2018
-
负责人:Deok-Ho Kim
-
依托单位:
Tissue Engineered Human Neuromuscular Junctions for Modeling Axonal Neuropathy
-
批准号:9235682
-
项目类别:
-
资助金额:$34.73万
-
财政年份:2016
-
负责人:Deok-Ho Kim
-
依托单位:
TISSUE ENGINEERED HUMAN NEUROMUSCULAR JUNCTIONS FOR MODELING AXONAL NEUROPATHY
-
批准号:10054199
-
项目类别:
-
资助金额:$35.64万
-
财政年份:2016
-
负责人:Deok-Ho Kim
-
依托单位:
Injectable myocardial matrix-grapheme composite hydrogels for functional cardiac tissue engineering
-
批准号:9034827
-
项目类别:
-
资助金额:$22.75万
-
财政年份:2016
-
负责人:Deok-Ho Kim
-
依托单位:
Nanopatterned 3D Vascularized Functional Muscle Patch
-
批准号:8636918
-
项目类别:
-
资助金额:$19.14万
-
财政年份:2014
-
负责人:Deok-Ho Kim
-
依托单位:
国内基金
海外基金
登录
查看更多内容
iPSC 来源 CAR-Ms 调控血管表型重塑促进创面无瘢痕再生的研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:曾文
-
依托单位:
基于CD47-SIRPα轴的工程化iPSC-ALMs在非小细胞肺癌治疗中的应用
-
批准号:2025JJ60504
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:罗丽莎
-
依托单位:
患者自体来源iPSC定向分化为抗逆型神经-血管单元移植治疗重度卒中后神经缺损致残
-
批准号:
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:林森
-
依托单位:
新型细胞因子复合体CIRB21联合CAR-EGFR修饰的通用型iPSC-NK细胞在奥希替尼耐药肺癌中的抗癌作用研究
-
批准号:MS25H160038
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:陈素梅
-
依托单位:
基于多成熟态人源iPSC诱导心肌细胞的抗心肌线粒体钙超载中药药效物质研究
-
批准号:QN25H280032
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2025
-
负责人:赵誉
-
依托单位:
IPSC来源的工程化三级淋巴结构类器官抗实体肿瘤的功能及机制研究
-
批准号:--
-
项目类别:青年科学基金项目
-
资助金额:--
-
批准年份:2024
-
负责人:王旭东
-
依托单位:
神经肽Y下调SERCA2触发房颤患者iPSC来源心肌细胞节律异常的分
子机制研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2024
-
负责人:蒋周芩
-
依托单位:
在患者iPSC来源类脑和小鼠中研究ASNS对大脑皮层神经分化的影响
-
批准号:
-
项目类别:省市级项目
-
资助金额:15.0万元
-
批准年份:2024
-
负责人:谢英俊
-
依托单位:
基于 iPSC-MNs 的常染色体隐性遗传性腓骨肌萎缩症
2S 型的致病机理研究
-
批准号:2024JJ5520
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2024
-
负责人:刘蕾
-
依托单位:
PFIC3基因治疗新策略:基于iPSC和基因编辑技术的小鼠脾脏内肝组织重建
-
批准号:
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2024
-
负责人:刘志峰
-
依托单位: