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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：
Tetsuro Wakatsuki
金额：
$ 34.94万
依托单位：
INVIVOSCIENCES, INC.
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

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

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.

心肌病有各种形式，包括肥厚型心肌病(HCM)，每500名患病率中有1名，可导致运动员心源性猝死，扩张型心肌病(DCM)，每5000名患病率中有1名，导致左心室增大，致心律失常的右室发育不良/心肌病(ARVD/C)，每1000名患病率中有1名，可导致心脏纤维化。美国医疗保健系统每年用于心血管治疗的费用超过2000亿美元。心血管治疗的疗效和毒性反应的个体间差异相当大。通过伴随诊断和新药的共同开发，可以实现安全有效的心血管药物。目的：利用患者的细胞构建工程心脏组织(EHTS)，建立重现患者心肌病的体外疾病模型。细胞、组织培养平台和新的心肌细胞分化方案的自动化将降低成本，提高为药物筛选和诊断开发而建立的疾病模型的生产率和重复性。基本原理：人类的IPSC技术将个性化医疗的“盘子里的疾病”想法变成了现实。然而，iPSC技术的成本减缓了它的进展。使用经济机器人的自动化干细胞培养产生针对患者的样本，以经济高效的方式进行药物筛选。近期目标：将威斯康星大学帕莱切克博士的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斯特兰德博士合作，评估使用该系统从肌营养不良患者分离的细胞制造EHT的可行性。建议项目：目标1开发高通量人心肌细胞分化优化系统及其用于EHT制备的自动化批量生产。目的2是为了验证基于EHT的肌营养不良模型的建立。成功的衡量标准：1)从一批干细胞培养中可重复地批量生产~400个EHT，2)使用大规模生产的CMS生产与生理相关的EHTS，3)重建患者的心脏病表型。其他影响：用于筛选干细胞培养条件的高通量平台可以应用于所有干细胞研究项目。技术的改进可以为临床上的细胞或工程化组织移植生产足够的心肌细胞。据估计，10亿个细胞足以治疗脑梗塞后的损伤。