Surface Proteins in the Differentiation of Stem Cells to Cardiomyocytes

描述(由申请人提供)： 心脏病是美国人的最大杀手。那些在心脏病发作中幸存下来的人再次发作、心力衰竭和中风的风险更高。因此，有必要开发修复心脏和/或改善心脏病发作后生活质量的方法。通过使用干细胞的再生医学概念作为一种恢复心脏功能的潜在疗法正受到人们的关注。目前临床细胞疗法的发展面临的障碍是：(1)用于选择纯细胞群体和跟踪分化的细胞表面标志物的可用性有限；(2)缺乏对心肌细胞体外分化和体内发育的相关性的了解。该项目的长期目标是将纯干细胞群体的功能与一组已定义的细胞表面标记联系起来。第一个授权期(K99)的主要目标是满足对信息丰富的细胞表面标记的需求，这些标记有助于确定特定的细胞类型、阶段和谱系。我将把从第一批授权期的研究中获得的经验和知识应用到第二阶段(Roo)的干细胞开发理解中。Roo阶段的目的是为了了解体外分化过程中的分子事件是否与体内心肌细胞发育过程中的分子事件相似。我的长期职业目标是领导一个独立的研究小组，利用分析技术将干细胞的基础科学研究和临床应用联系起来。这项研究计划是专门为利用我的分析专长而设计的，同时提供相关的生物学背景，以获得必要的新知识和技能，最大限度地在生物学背景下使用分析方法。约翰霍普金斯大学的培训环境特别适合这项研究，因为它可以获得最先进的仪器，拥有专业知识的导师，以及支持临床相关研究讨论的论坛。相关性：当前建议的重点是确定特定的细胞表面蛋白标记，以帮助临床医生和研究人员了解干细胞分化的机制，无论是在动物体内还是在培养中。将产生适用于心血管再生医学的干细胞群体的特定选择、丰富和跟踪的可访问标记。(摘要结束)

DESCRIPTION (provided by applicant): Heart disease is the single largest killer of Americans. Those that survive a heart attack have a higher risk of another attack heart failure, and stroke. Consequently, there is a need to develop approaches for repairing the heart and/improving the quality of life after a heart attack. The concept of regenerative medicine through the use of stem cells is gaining attention as a potential therapy for restoring cardiac function. Hurdles currently faced in the development of cellular therapies for the clinic are (1) the limited availability of cell surface markers for selecting pure cell populations and for tracking differentiation and (2) the lack of knowledge of how in vitro differentiation and in vivo development of cardiomyocytes correlate. The long term goal of this project is to correlate the function of a pure population of stem cells with a panel of defined cell surface markers. The major objective of the first granting period (K99) is to address the need for informative cell surface markers that are useful for characterizing specific cell types, stages, and lineages. I will apply the experience and knowledge gained from the research in the first granting period to understanding stem cell development in the second phase (ROO). The aims of the ROO phase are designed to develop an understanding of whether the molecular events during in vitro differentiation mimic those during in vivo development of cardiomyocytes. My long term career goal is to lead an independent research group that utilizes analytical technologies to bridge basic science research and clinical applications of stem cells. This research plan is specifically designed to take advantage of my analytical expertise while providing a relevant biological context to acquire new knowledge and skills necessary maximize the use of analytical methods within the context of biology. The training environment at Johns Hopkins is especially suited to this research due to the access to state-of-the art instrumentation, mentors with specialized expertise, and the forum to support discussion of clinically relevant research. Relevance: The focus of the current proposal is to identify specific cell surface protein markers that will aid clinicians and researchers in understanding the mechanisms of stem cell differentiation, both within the animal and in culture. Accessible markers for the specific selection, enrichment, and tracking of stem cell populations appropriate for cardiovascular regenerative medicine will be generated. (End of Abstract)