Molecular Imaging of Novel Cardiomyocyte Stem Cells

新型心肌细胞干细胞的分子成像

• 批准号: 7118127
• 负责人: Steven N. Ebert
• 金额: $ 18.85万
• 依托单位: UNIVERSITY OF CENTRAL FLORIDA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-22 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7118127
• 关键词: bioimaging /biomedical imaging; bioluminescence; cardiac myocytes; cell differentiation; cell proliferation; embryonic stem cell; flow cytometry; gene expression; heart function; heart imaging /visualization /scanning; immunofluorescence technique; laboratory mouse; luciferin monooxygenase; magnetic resonance imaging; methyltransferase; muscle satellite cell; musculoskeletal disorder therapy; myocardial infarction; regeneration; reporter genes; stem cell transplantation; therapy design /development; tissue /cell culture

DESCRIPTION (provided by applicant): Development and application of non-invasive imaging techniques to physically and functionally assess the potential of novel cardiomyocyte stem cells to regenerate damaged myocardium have clear clinical significance. Repair and replacement of damaged cardiac muscle tissue is a key limitation in the recovery from ischemic and other forms of heart disease, the leading cause of death in the United States. New strategies for regenerating damaged cardiac muscle are urgently needed and could be readily translated to the clinical setting if first shown to be effective in animal models. The proposal outlined here will demonstrate the feasibility of using molecular imaging techniques in vivo to evaluate our novel stem cell-based strategy for cardiac regenerative medicine. This research proposal directly addresses both of the stated goals of the initiative outlined in RFA-HL-04-003 (Cellular and Molecular Imaging of the Cardiovascular, Pulmonary, and Hematopoetic Systems): (1) Detect and quantify molecular and cellular pathways that regulate heart function...(we describe and will further characterize a novel cardiomyocyte differentiation pathway), and (2) Develop new methods for cell tracking in vivo for applications in cell-based therapeutics...(we will transplant novel cardiomyocyte stem cells into damaged hearts and track them in vivo using advanced magnetic resonance and bioluminescent imaging methods). Our data indicate that cardiac cells transiently expressing the enzyme, Phenylethanolamine n-methyltransferase (Pnmt), ultimately become myocytes that contribute substantially to pacemaking, conduction, and working myocardium. Thus, Pnmt serves as a novel marker of cardiomyocyte stem cells (Pnmt+ cells) in the developing heart. We will test the idea that Pnmt+ cells can be selectively isolated and transplanted into damaged cardiac regions where they will be monitored both physically (location) and physiologically (function) using non-invasive molecular and cellular imaging techniques to evaluate the potential of these cells to regenerate cardiac muscle tissue in vivo. Three specific aims are proposed to accomplish this goal: Aim 1: Isolate and characterize Pnmt-nEGFP+ cells from cardiac-differentiated embryonic stem cells. Aim 2: In vivo magnetic resonance imaging (MRI) of transplanted cardiomyocyte stem (Pnmt+) cells. Aim 3: In vivo bioluminescence imaging (BLI) of transplanted cardiomyocyte stem (Pnmt+) cells. (End of Abstract)

描述（由申请人提供）： 开发和应用非侵入性成像技术来物理和功能评估新型心肌细胞干细胞再生受损心肌的潜力具有明确的临床意义。受损心肌组织的修复和替换是缺血性心脏病和其他形式的心脏病恢复的一个关键限制，而缺血性心脏病是美国的主要死亡原因。迫切需要再生受损心肌的新策略，如果首先在动物模型中显示有效，则可以很容易地将其转化为临床环境。这里概述的提案将证明使用体内分子成像技术来评估我们基于干细胞的新型心脏再生医学策略的可行性。该研究提案直接解决 RFA-HL-04-003（心血管、肺和造血系统的细胞和分子成像）中概述的该计划的两个既定目标：（1）检测和量化调节心脏功能的分子和细胞途径......（我们描述并将进一步表征一种新型心肌细胞分化途径），以及（2）开发细胞分化的新方法 体内跟踪在细胞治疗中的应用...（我们将把新型心肌细胞干细胞移植到受损的心脏中，并使用先进的磁共振和生物发光成像方法在体内跟踪它们）。我们的数据表明，短暂表达苯乙醇胺 n-甲基转移酶 (Pnmt) 的心肌细胞最终成为对起搏、传导和工作心肌做出重大贡献的心肌细胞。因此，Pnmt 可作为发育中心脏中心肌干细胞（Pnmt+ 细胞）的新标记物。我们将测试这样的想法：可以选择性地分离 Pnmt+ 细胞并将其移植到受损的心脏区域，并使用非侵入性分子和细胞成像技术对它们的物理（位置）和生理（功能）进行监测，以评估这些细胞在体内再生心肌组织的潜力。 为实现这一目标，提出了三个具体目标： 目标 1：从心脏分化的胚胎干细胞中分离并表征 Pnmt-nEGFP+ 细胞。目标 2：移植的心肌干细胞 (Pnmt+) 的体内磁共振成像 (MRI)。目标 3：移植的心肌干细胞 (Pnmt+) 的体内生物发光成像 (BLI)。 （摘要完）