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

本提案是应NIH/NHLBI关于建立“人类诱导的心血管疾病多能干细胞生物库”(以下简称“生物库”)的要求而准备的。拟议的斯坦福心血管研究所(SCVI)生物库将管理和管理扩大的人类诱导多能干细胞(IPSC)系集合，并为研究人员提供使用标准化方案产生的IPSC材料，总体目标是促进IPSC技术在心血管研究中的继续采用和发展。 人类ipscs给疾病建模、药物筛选和治疗研究带来了革命性的变化。然而，人们也认识到，对专门技术知识的需要和相关费用在很大程度上阻碍了个别研究实验室在其调查中采用IPSC模式，特别是在需要多个细胞系的研究中。为了解决这一瓶颈，拟议的生物资料库将维持我们现有的IPSC系列，并通过招募1000名健康、肥厚型心肌病(HCM)、扩张型心肌病(DCM)捐赠者以及不同种族/民族背景(非裔美国人、亚洲人、拉美裔人和白人)来进一步扩大IPSC的收集。我们将继续以最低的运输成本向调查人员提供细胞材料，并在我们的公共网站上开放访问未确认的特征数据。 在过去的五年中，我们的团队已经向心血管研究界的250多名研究人员交付了超过2500瓶IPSC和IPSC来源的心肌细胞(IPSC-CMS)。拟议的SCVI生物库将继承目前SCVI IPSC生物库的现有组织资产和设施，该生物库于2014年通过R24机制(R24 HL117756；4/15/2014-3/31/2020；免费延期)在为期5年的NHLBI支持下建立。SCVI生物库位于斯坦福校区，占地2500平方米。FT的现代化设施，完全致力于拟议的生物库服务和沙箱学术研究活动。斯坦福大学提供支持性的制度环境和世界一流的基础设施，包括RedCap(研究电子数据捕获)和STRIDE(斯坦福翻译研究集成数据库环境)临床信息数据管理系统，校园范围的高速安全网络，以及用于资源管理的安全内部服务器。 我们已经组建了一支由专家调查人员和熟练工作人员组成的团队，他们拥有来自我们SCVI生物库的适当经验和培训。我们的领导团队、内部科学顾问委员会和三个核心员工团队(行政、技术和招聘团队)随时准备与NIH/NHLBI和外部顾问合作，以满足生物库的运营和科学需求。将特别注重资源管理，以维持现有资源并预期未来的扩展。我们拥有丰富的经验来处理服务请求和管理材料转移，样品运输和物流。在拟议的SCVI生物仓库中，我们将与NIH合作，通过编写操作手册(MOP)和创建可跟踪的自动请求系统来进一步编纂我们的专业知识，这将使我们应对扩大IPSC交付以促进未来进展的持续挑战。

This proposal is prepared in response to the NIH/NHLBI request to establish a "Biorepository of Human Induced Pluripotent Stem Cells for Cardiovascular Diseases" (hereafter "Biorepository"). The proposed Stanford Cardiovascular Institute (SCVI) Biorepository will curate and manage an expanded collection of human induced pluripotent stem cell (iPSC) lines and provide investigators with iPSC materials generated using standardized protocols, with the overall objective of promoting the continued adoption and development of iPSC technology in cardiovascular research. Human iPSCs have revolutionized disease modeling, drug screening, and therapeutic research. However, it is also recognized that the need for specialized technical expertise and the associated cost have largely prevented individual research laboratories from adopting iPSC models in their inquiries, particularly in studies requiring multiple cell lines. To address this bottleneck, the proposed Biorepository will maintain our existing collection of iPSC lines and further expand the collection of iPSCs by recruiting 1,000 healthy, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) donors of both sexes and diverse racial/ethnic backgrounds (African Americans, Asians, Hispanics, and Whites). We will continue to provide cell materials to investigators at minimal shipping costs as well as open access to de- identified characterization data on our public website. In the past five years, our team has delivered over 2,500 vials of iPSCs and iPSC-derived cardiomyocytes (iPSC-CMs) to over 250 investigators in the cardiovascular research community. The proposed SCVI Biorepository will inherit established organizational assets and facilities of the present SCVI iPSC Biobank, which was established in 2014 under a 5-year NHLBI support through the R24 mechanism (R24 HL117756; 4/15/2014 - 3/31/2020; no-cost extension). The SCVI Biorepository is located on the Stanford campus and occupies 2,500 sq. ft of modern facilities that are wholly dedicated to the proposed biobanking service and sandboxed from academic research activities. Stanford offers a supportive institutional environment and world-class infrastructure, including the REDCap (Research Electronic Data Capture) and STRIDE (Stanford Translational Research Integrated Database Environment) clinical informatics data management systems, campus-wide high-speed secure networks, and secure internal servers for resource management. We have assembled a team of expert investigators and skilled staff with suitable experience and training from our SCVI Biobank. Our leadership team, internal scientific advisory board, and three core staff teams (Administrative, Technical, and Recruitment teams) stand ready to work with NIH/NHLBI and external advisors to tackle operational and scientific needs of the Biorepository. Particular focus will be given to resource management to maintain existing resources and anticipate future expansion. We possess ample experience to handle service requests and administer material transfer, sample shipment, and logistics. In the proposed SCVI Biorepository, we will work with NIH to further codify our expertise by Authoring a Manual of Operations (MOP) and creating an automated trackable request system, which will us meet ongoing challenges of scaling up iPSC delivery to promote future advances.