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: 8927657
• 负责人: Tetsuro Wakatsuki
• 金额: $ 34.94万
• 依托单位: INVIVOSCIENCES, INC.
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/8927657
• 关键词: American; Arrhythmogenic Right Ventricular Dysplasia; Automation; Biological Markers; Biomedical Engineering; Blood; Blood Vessels; Cardiac; Cardiac Death; Cardiac Myocytes; Cardiomyopathies; Cardiovascular system; Cell Count; Cell Culture Techniques; Cell Differentiation process; Cell Line; Cells; Clinic; Clinical; Collaborations; Companions; Cultured Cells; Development; Diagnostic; Differentiation Antigens; Dilated Cardiomyopathy; Disease; Disease model; Drug toxicity; Economics; Engineering; Evaluation; Future; Goals; Government; Health; Healthcare Systems; Heart; Heart Diseases; Human; Human Engineering; Hypertrophic Cardiomyopathy; In Vitro; Individual; Infarction; Injury; Laboratories; Lead; Left ventricular structure; Liquid substance; Measures; Medicine; Methods; Mission; Modification; Muscular Dystrophies; Myocardium; Outcome; Patient observation; Patients; Persons; Pharmaceutical Preparations; Pharmacogenomics; Phase; Phenotype; Physiological; Preclinical Drug Evaluation; Prevalence; Production; Productivity; Protocols documentation; Reproducibility; Research; Robot; Robotics; Sampling; Skeletal Muscle; Stem Cell Research; Stem cells; System; Technology; Testing; Time; Tissue Engineering; Tissues; Toxic effect; Translating; Transplantation; Troponin T; Universities; Urine; Wisconsin; Work; base; cellular engineering; companion diagnostics; coronary fibrosis; cost; cost effective; disease phenotype; flexibility; improved; medical schools; model development; novel; personalized medicine; personalized screening; phase 1 study; professor; reconstitution; respiratory; response; scale up; screening; stem cell technology; success; sudden cardiac death; tissue/cell culture; tool

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（申请人提供）：心肌病具有各种形式1000患病率会导致心脏纤维化。美国医疗保健系统每年用于心脏血管治疗每年超过2000亿美元。对于心血管治疗，功效和毒性疗效的个体间变异性相当大。可以通过共同开发伴侣诊断和新型药物来实现安全有效的心血管医学。目的：开发体外疾病模型，以概括使用患者细胞产生的工程心脏组织（EHT）中患者的心肌病。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，提高生产力和可重现性，从而产生这些疾病模型进行药物筛查和诊断开发。理由：人类IPSC技术将“菜肴中的疾病”转移到了个性化医学的现实中。然而，IPSC技术的成本减慢了进步。具有经济机器人技术的自动干细胞培养可以有效地产生特定于患者的药物筛查样品。直接目标：翻译威斯康星大学Palecek博士学术实验室中开发的心脏分化方案，为商业上可行的格式。将使用该系统与从肌肉营养不良患者分离的细胞进行EHT制造的可行性将与威斯康星州医学院的Strande博士合作评估。拟议的项目：AIM 1是高通量人类心肌细胞分化优化系统的发展及其自动质量生产以进行EHT制造。目的2是证明基于EHT的肌肉营养不良模型开发。成功度量：将通过1）从一批干细胞培养物中可重复产生〜400 EHT产生的质量生产2）使用质量产生的CMS生产生理相关的EHT，3）患者中心脏病表型的重新建立。其他影响：用于筛查干细胞培养条件的高通量平台可以应用于干细胞研究的所有项目。技术的修饰可以为诊所中的细胞或工程组织移植产生足够的心脏细胞。估计有十亿个细胞是足够数量的细胞来治疗梗塞后损伤。