Human Embryonic Stem Cell Derived Cardiac Progenitors

人胚胎干细胞衍生的心脏祖细胞

• 批准号: 7151620
• 负责人: Paul Esteso
• 金额: $ 4.58万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7151620
• 关键词: cardiac myocytes; cell differentiation; cell proliferation; flow cytometry; gene expression; genetic markers; heart transplantation; human embryonic stem cell line; immunocytochemistry; microarray technology; myocardial infarction; polymerase chain reaction; predoctoral investigator; regeneration; therapy design /development; transfection

DESCRIPTION (provided by applicant): The hypoxic insult that occurs in myocardial infarctions damages the myocardium it nourishes, often leading to tissue necrosis. The necrotic area becomes an inelastic scar, often leading to ventricular hypertrophy and congestive heart failure. The purpose of my research under the NRSA fellowship is to study presidentially approved WAO1 human embryonic stem (hES) cells to define populations of cardiac progenitor cells (CPCs) suitable for transplantation into the site of myocardial injury. Thus, I hope to prevent myocardial degeneration and maintain functionality. The characteristics of mouse embryonic stem cell derived CPCs have been defined in my laboratory, and will serve as a basis to establish hES cell derived CPC populations. My first aim will be to establish the genetic markers characteristic of these cells in vivo and in vitro. My second aim is to determine gene expression levels to pinpoint CPCs temporal location during hES cell differentiation. My third aim is to establish a mechanism for selection of CPCs into pure populations. My fourth aim is to evaluate purified hES CPCs proliferative potential in vitro and in vivo. Future goals would include testing the safety and therapeutic potential of these cells in the pig myocardial infarction transplant model.

描述（由申请人提供）：心肌梗塞中发生的缺氧损伤会损害其所滋养的心肌，通常导致组织坏死。坏死区域变成无弹性疤痕，常常导致心室肥大和充血性心力衰竭。我在 NRSA 奖学金下的研究目的是研究总统批准的 WAO1 人类胚胎干 (hES) 细胞，以确定适合移植到心肌损伤部位的心脏祖细胞 (CPC) 群。因此，我希望能够防止心肌退化并维持功能。小鼠胚胎干细胞衍生的 CPC 的特征已在我的实验室中确定，并将作为建立 hES 细胞衍生的 CPC 群体的基础。我的首要目标是在体内和体外建立这些细胞的遗传标记特征。我的第二个目标是确定基因表达水平，以查明 CPC 在 hES 细胞分化过程中的时间位置。我的第三个目标是建立一个将CPC选入纯种群的机制。我的第四个目标是评估纯化的 hES CPC 的体外和体内增殖潜力。未来的目标包括在猪心肌梗塞移植模型中测试这些细胞的安全性和治疗潜力。