BIOREPOSITORY OF HUMAN INDUCED PLURIPOTENT STEM CELLSFORCARDIOVASCULAR DISEASES (BHIPSC-CVD)- TASK A. CORE STUDY OPERATIONS

自2006年发现以来，人类诱导多能干细胞(IPSCs)被应用于三个主要领域：疾病模型、药物开发和再生治疗。这些细胞具有自我更新的固有特性，在适当的生长和信号因子的作用下，它们可以分化为任何类型的细胞，如诱导多能干细胞来源的心肌细胞(IPSC-CMS)，这些细胞保留了来源个体的基因，并在体外表现出疾病的表型特征。IPSC和IPSC-CMS的使用使研究人员能够了解疾病机制，筛选药物毒性，并预测患者对新药的反应。为了促进IPSC技术在心血管研究中的可获得性和发展，斯坦福大学心血管研究所(SCVI)人类诱导多潜能干细胞心血管疾病生物资源库(BhiPSC-CVD)管理和管理一系列人IPSC系，并使用标准化方案为研究人员提供生成的IPSC材料。BhiPSC-CVD的具体目标是：1)招募不同种族和民族的扩张型心肌病、肥厚型心肌病和健康患者，特别注重少数族裔(如非洲裔美国人、亚洲人、西班牙裔人和白人)；2)从患者池或研究人员提供的未确认身份的血液样本中创建和维护IPSC系；3)使用IPSC及其衍生物(如IPSC-CMS)进行心脏毒性药物筛选；4)获取患者病史和转录组信息；以及5)为NHLBI调查人员提供必要的IPSC专业知识、服务和资源。总体而言，BhiPSC-CVD使研究能够更好地了解病理生物学和对治疗的反应的个体差异，以及开发和优化治疗心血管疾病的新治疗策略。

Since their 2006 discovery, human induced pluripotent stem cells (iPSCs) are applied in three major areas: disease modeling, drug discovery, and regenerative therapy. The cells hold inherent properties to self-renew and with the appropriate growth and signaling factors, they can differentiate into any cell type, such as induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) that retain the genotype of individuals from whom they were derived from and exhibit the phenotypic features of disease in vitro. The use of iPSCs and iPSC-CMs enable researchers to understand disease mechanisms, screen for drug toxicity, and predict patient responses to new drugs. To promote the availability and development of iPSC technology in cardiovascular research, the Stanford Cardiovascular Institute (SCVI) Biorepository of Human Induced Pluripotent Stem Cells for Cardiovascular Diseases (BhiPSC-CVD) curates and manages a collection of human iPSC lines, as well as provides investigators with generated iPSC materials using standardized protocols. The specific aims of BhiPSC-CVD are to: 1) recruit dilated cardiomyopathy, hypertrophic cardiomyopathy, and healthy patients from diverse racial and ethnic backgrounds with a particular emphasis on minorities (e.g., African Americans, Asians, Hispanics, and Whites); 2) create and maintain iPSC lines from the patient pool or investigator-provided de-identified blood samples; 3) perform cardiotoxicity drug screening using iPSCs and their derivatives (e.g., iPSC-CMs); 4) acquire patient medical history and transcriptome information; and 5) provide NHLBI investigators with the necessary iPSC expertise, services, and resources. Overall, BhiPSC-CVD enables research towards greater understanding of individual differences in pathobiology and in response to treatment, as well as developing and optimizing novel therapeutic strategies to treat and cure cardiovascular disease.