EFRI-CBE: Engineering of cardiovascular cellular interfaces and tissue constructs

EFRI-CBE：心血管细胞界面和组织结构的工程

• 批准号: 0735551
• 负责人: Beth Pruitt
• 金额: $ 200万
• 依托单位: Stanford University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0735551&HistoricalAwards=false
• 关键词: EFRI; CBE; Engineering; cardiovascular; cellular

PI name: B.L. Pruitt Institution: Stanford University Proposal Number: 0735551 EFRI-CBE: Engineering of Cardiovascular Cellular Interfaces and Tissue ConstructsAbstractCardiac cells and tissue are ideal targets for regenerative medicine and fundamental studies of the interplay of cellular and biomolecular level signaling and response for several reasons. First, observation of successful stem cell differentiation to cardiac myocytes is facilitated by readily identifiable immunohistochemical markers as well as characteristic electrical action potentials and mechanical contractions. Second, explanted cells in culture lose their morphology and organization in the absence of drugs or electromechanical stimulation, suggesting that cellular organization is dependent on these cues. Last, myocardium damaged during a heart attack does not regenerate and the weakened muscle results in heart failure. Fundamental understanding of how cardiac myocytes and heart tissue can be regenerated is essential to creating successful therapies for patients with heart disease (affecting 71 million Americans). Recently, several studies have shown that stem cells may offer regenerative potential through direct injection of cells into the damaged myocardium or in situ repair using engineered tissue grafts.The Intellectual Merit of this project lies in the development of basic knowledge and models for cell response to environmental cues. Pluripotent cell responses to changes in environment offer a testbed for characterizing the thresholds and mechanisms of environmental adaptation and remodeling. The outcomes of the baseline and coupled experiments will be made available as a database for other researchers. Models and results will be disseminated by publication and seminars for researchers in the field as well as public seminar forums.The Broader Impacts of this work lie in the enhanced knowledge of cell signaling and differentiation, the role of culture environmental parameters in tissue engineering, and the enhanced design guidance and technology developed which will ultimately enable regenerative therapies for victims of heart disease. Topics of this research will be incorporated in modules for teaching basic engineering and materials courses and the Principal Investigators (PIs) will recruit undergraduates for research experiences in their labs. The PIs actively participate in outreach, undergraduate research opportunities, and research experience for teacher programs and will expand these efforts related to this project. A workshop on the research topics will be held in the final year of the project.

PI姓名：B.L. Pruitt机构：斯坦福大学提案号：0735551 EFRI-CBE：心血管细胞界面和组织结构工程摘要心脏细胞和组织是再生医学和细胞与生物分子水平信号和反应相互作用的基础研究的理想靶点。首先，通过容易识别的免疫组织化学标记以及特征性电动作电位和机械收缩促进了干细胞向心肌细胞成功分化的观察。第二，在没有药物或机电刺激的情况下，培养中的凋亡细胞失去了它们的形态和组织，这表明细胞组织依赖于这些线索。最后，心脏病发作时受损的心肌不能再生，而衰弱的肌肉会导致心力衰竭。对心肌细胞和心脏组织如何再生的基本理解对于为心脏病患者（影响7100万美国人）创造成功的治疗方法至关重要。近年来，一些研究表明，干细胞可以通过直接注射到受损心肌或使用工程化组织移植物原位修复来提供再生潜能。本项目的智力价值在于发展细胞对环境信号反应的基础知识和模型。多能细胞对环境变化的反应为表征环境适应和重塑的阈值和机制提供了试验平台。基线和耦合实验的结果将作为数据库提供给其他研究人员。模型和结果将通过出版物和为该领域研究人员举办的研讨会以及公共研讨会论坛进行传播。这项工作的更广泛影响在于增强了对细胞信号传导和分化的认识，培养环境参数在组织工程中的作用，以及增强了设计指导和开发的技术，最终将使心脏病患者的再生疗法成为可能。这项研究的主题将被纳入基础工程和材料课程的教学模块，主要研究人员（PI）将招募本科生在他们的实验室进行研究。PI积极参与外展，本科生研究机会和教师计划的研究经验，并将扩大与此项目相关的这些努力。将在项目的最后一年举办有关研究主题的研讨会。