Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia

用于测试药物引起的心律失常的工程人体心脏切片

• 批准号: 10616266
• 负责人: KENNETH Richard BOHELER
• 金额: $ 8.63万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10616266
• 关键词: 3-Dimensional; Adipocytes; Adipose tissue; Adult; Aging; Arrhythmia; Arrhythmogenic Right Ventricular Dysplasia; Biological; CD36 gene; Cardiac; Cardiac Myocytes; Cells; Development; Diagnosis; Disease; Disease model; Drug Screening; Engineering; Environment; Fatty Acids; Fatty acid glycerol esters; Goals; Hearing; Heart; Human; Human Engineering; Influentials; Metabolic; Modeling; Myocardial; Natural regeneration; Pathologic; Patients; Phenotype; Research; Role; Slice; Source; Stimulant; Tachyarrhythmias; Testing; Tissues; Work; cardiac tissue engineering; drug testing; fetal; human model; human stem cells; induced pluripotent stem cell derived cardiomyocytes; parent grant; response; stem cells

The parent grant “Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia” aims to develop an engineered hear slice (EHS) model that will have the ability to test for drug-induced, cardiac tachyarrhythmias. The cardiomyocytes in the EHS model are obtained from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). While hiPSC-CMs are a promising cell source for cardiomyocytes, these cells are limited in their maturation state. hiPSC- CMs are currently fetal-like in their development, and require stimulants to achieve an adult-like phenotype. The parent grant focuses on the use of electromechanical, biological, and maturation medias to attain such a phenotype in hiPSC-CMs. This leads to the goal of this supplemental research, which is to apply an alternate stimulant to aid in the maturation of hiPSC-CMs. This stimulant is the secretome from adipocytes (fat generating cells). The adipocytes will serve as a source of fatty acids, which have proven to be influential in the metabolic maturation of cardiomyocytes. The specific aim of this supplemental work is to investigate the beneficial (or pathological) role of the secretome from adipocytes derived from human Adipose-Derived Stem Cells (hASCs) as a maturation stimulant for hiPSC-CMs that are either untreated, sorted for CD36+ (a metabolic maturation marker), or derived from patients diagnosed with arrhythmogenic right ventricular cardiomyopathy. The supplemental research will also examine whether the responses of the hiPSC-CMs are enhanced in a more 3D environment consisting of decellularized cardiac tissue.

家长资助的“用于检测药物性心律失常的工程人类心脏切片”旨在

项目成果

Understanding Arrhythmogenic Cardiomyopathy: Advances through the Use of Human Pluripotent Stem Cell Models.

• DOI: 10.3390/genes14101864
• 发表时间: 2023-09-25
• 期刊: GENES
• 影响因子: 3.5
• 作者: Chua, Christianne J.;Morrissette-McAlmon, Justin;Tung, Leslie;Boheler, Kenneth R.
• 通讯作者: Boheler, Kenneth R.