MASS PRODUCTION OF PERSONALIZED HUMAN ENGINEERED HEART TISSUES

大规模生产个性化人体工程心脏组织

基本信息

  • 批准号:
    8927657
  • 负责人:
  • 金额:
    $ 34.94万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-09-15 至 2017-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Cardiomyopathy has various forms including hypertrophic cardiomyopathy (HCM), 1 in 500 prevalence, could cause sudden cardiac death in athletes, Dilated Cardiomyopathy (DCM), 1 in 5000 prevalence, results in an enlarge left ventricle, Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C), 1 in 1000 prevalence, causes cardiac fibrosis. Yearly over $ 200 billion is spent by American healthcare system for cardio- vascular treatment. Inter-individual variability in efficacy and toxicity respone is rather large for cardiovascular treatments. Safe and effective cardiovascular medicine can be achieved by co-development of companion diagnostics and novel drugs. Objective: To develop in vitro disease model that recapitulate individual patient's cardiomyopathy in engineered heart tissues (EHTs) generated using the patient's cells. The automation of cell, tissue culture platform, and novel cardiomyocytes differentiation protocol will reduce cost, increase productivity and reproducibility of generating those disease models for drug screening and diagnostics development. Rationale: The human iPSC technology moved "Diseases in a dish" idea to reality for personalized medicine. Yet the cost of iPSC technology slowed its progress. Automated stem cell culture with an economic robotics produces patient-specific samples for drug screening cost effectively. Immediate goal: To translate cardiac differentiation protocol developed in the academic labs of Dr. Palecek at University of Wisconsin into a commercially viable format. Feasibility of using the system for EHT fabrication with cells isolated from muscular dystrophy patients will be evaluated in collaboration with Dr. Strande at the Medical College of Wisconsin. Proposed project: Aim 1 is the development of high-throughput human cardiomyocytes differentiation optimization system and their automated mass-production for EHT fabrication. Aim 2 is to demonstrate EHT based muscular dystrophy model development. Measure of Success: It will be measured by 1) reproducible mass-production of ~400 EHT production from a batch of stem cell culture 2) production of physiologically relevant EHTs using mass produced CMs, 3) reconstitution of cardiac disease phenotype in patient. Additional Impact: High-throughput platform for screening stem cell culture conditions can be applied to all projects of stem cell research. A modification of technology could produce enough cardiac cells for cell or engineered tissue transplant in clinic. One billion cells were estimated to be a sufficient number of cells to treat post infarct injury.
描述(由申请人提供):心肌病有多种形式,包括肥厚性心肌病(HCM),患病率为五百分之一,可能导致运动员心源性猝死;扩张型心肌病(DCM),患病率为五分之一,导致左心室扩大;致心律失常右心室发育不良/心肌病 (ARVD/C),患病率为千分之一,会导致心脏病纤维化。美国医疗保健系统每年花费超过 2000 亿美元用于心血管治疗。对于心血管治疗来说,疗效和毒性反应的个体间差异相当大。通过共同开发伴随诊断和新药可以实现安全有效的心血管医学。目的:开发体外疾病模型,在使用患者细胞生成的工程心脏组织(EHT)中重现个体患者的心肌病。细胞、组织培养平台和新型心肌细胞分化方案的自动化将降低成本,提高生成用于药物筛选和诊断开发的疾病模型的生产率和可重复性。理由:人类 iPSC 技术将“一道菜中的疾病”的想法变为现实,实现个性化医疗。然而 iPSC 技术的成本减缓了其进展。采用经济型机器人技术的自动化干细胞培养可以经济有效地生产患者特异性样本,用于药物筛选。近期目标:将威斯康星大学 Palecek 博士学术实验室开发的心脏分化方案转化为商业上可行的格式。将与威斯康星医学院的 Strande 博士合作评估使用该系统对从肌营养不良症患者中分离出的细胞进行 EHT 制造的可行性。拟议项目:目标 1 是开发高通量人类心肌细胞分化优化系统及其用于 EHT 制造的自动化大规模生产。目标 2 是展示基于 EHT 的肌营养不良模型开发。成功的衡量标准:通过以下方式衡量:1) 从一批干细胞培养物中可重复地大规模生产约 400 个 EHT,2) 使用批量生产的 CM 生产生理相关的 EHT,3) 重建患者的心脏病表型。附加影响:筛选干细胞培养条件的高通量平台可应用于干细胞研究的所有项目。技术的改进可以产生足够的心脏细胞用于临床细胞或工程组织移植。据估计,十亿个细胞足以治疗梗塞后损伤。

项目成果

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Tetsuro Wakatsuki其他文献

Tetsuro Wakatsuki的其他文献

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{{ truncateString('Tetsuro Wakatsuki', 18)}}的其他基金

Diagnostic Tools for Targeted Heart Failure Treatments
心力衰竭靶向治疗的诊断工具
  • 批准号:
    10546035
  • 财政年份:
    2022
  • 资助金额:
    $ 34.94万
  • 项目类别:
HLS-Cardiac Safety AI Trained Human Heart and Micro Heart Model
HLS-心脏安全 AI 训练的人类心脏和微心脏模型
  • 批准号:
    9764845
  • 财政年份:
    2019
  • 资助金额:
    $ 34.94万
  • 项目类别:
An Aging Heart Model for Drug Discovery
用于药物发现的衰老心脏模型
  • 批准号:
    9331414
  • 财政年份:
    2016
  • 资助金额:
    $ 34.94万
  • 项目类别:
Engineered Tissue Based Phenotypic Screening of Mixture based Libraries
基于工程组织的混合物库表型筛选
  • 批准号:
    9145632
  • 财政年份:
    2015
  • 资助金额:
    $ 34.94万
  • 项目类别:
Engineered Tissue Based Phenotypic Screening of Mixture based Libraries
基于工程组织的混合物库表型筛选
  • 批准号:
    9221892
  • 财政年份:
    2015
  • 资助金额:
    $ 34.94万
  • 项目类别:
Engineered Tissue Based Phenotypic Screening of Mixture based Libraries
基于工程组织的混合物库表型筛选
  • 批准号:
    9047064
  • 财政年份:
    2015
  • 资助金额:
    $ 34.94万
  • 项目类别:
MASS PRODUCTION OF PERSONALIZED HUMAN ENGINEERED HEART TISSUES
大规模生产个性化人体工程心脏组织
  • 批准号:
    8780580
  • 财政年份:
    2014
  • 资助金额:
    $ 34.94万
  • 项目类别:
Engineered tissue-based, high-throughput compound profiling
基于组织的工程化高通量化合物分析
  • 批准号:
    8252293
  • 财政年份:
    2009
  • 资助金额:
    $ 34.94万
  • 项目类别:
Engineered tissue-based, high-throughput compound profiling
基于组织的工程化高通量化合物分析
  • 批准号:
    8619035
  • 财政年份:
    2009
  • 资助金额:
    $ 34.94万
  • 项目类别:
Engineered tissue-based, high-throughput compound profiling
基于组织的工程化高通量化合物分析
  • 批准号:
    8545867
  • 财政年份:
    2009
  • 资助金额:
    $ 34.94万
  • 项目类别:

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    2023
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