Cellular and Molecular MRI of Stem Cell Viability

描述(由申请人提供)：一种体内成像移植细胞植入受损心肌的方法将使细胞治疗的准确评估成为可能。植入是一个复杂的生物学过程，包括细胞存活和受体组织的功能恢复。虽然MRI已成为追踪体外标记细胞的主要方法之一，但MRI不能评估有关细胞活性的明确信息。为了解决这一关键问题，本提案将描述在体内实施细胞和分子磁共振成像以显示移植的小鼠胚胎干细胞(MESC)的存活情况以及在小鼠心肌梗死模型中损伤心肌的功能恢复。为了实现这一目标，将整合新的磁共振成像方法、创新的细胞和分子技术以及广泛的已有方法，对三个特定目标进行系统研究：特定目标1-活体细胞磁共振成像将能够使用新的非共振磁共振序列准确地评估移植的mESC的生存能力。特定目的2-利用MRI报告基因和靶向造影剂对基因工程细胞的体内分子磁共振检测移植的mESC的活性。特定目的3-存活的mESC将促进受损心肌的功能恢复。这项研究计划将心血管成像和干细胞生物学的多学科研究结合在一起。这一方法使磁共振成像和干细胞生物学的创新方法得以融合，以解决一个关键的基本问题：干细胞移植到心肌中后的细胞生存能力。这一建议补充了磁共振成像的高空间和时间分辨率，并利用细胞和分子技术放大了磁共振成像的敏感性。在这项研究结束后，一个集成的MRI平台将允许对细胞活性和心肌修复进行双重评估。研究表明，心肌梗死在充血性心力衰竭(CHF)的发生发展中起着重要作用。充血性心力衰竭的发病率现在正达到流行的程度。胚胎干细胞已显示出修复受损心肌的能力。一种评估移植细胞存活的非侵入性方法将解决这一新的治疗方案中的一个基本问题。

DESCRIPTION (provided by applicant): An in vivo method to image the engraftment of the transplanted cells in the injured myocardium will enable precise evaluation of cell therapy. Engraftment is a complex cascade of biological processes including cell survival and functional restoration of the recipient tissue. Although MRI has become one of the predominant modalities to track ex vivo labeled cells, definitive information on cellular viability can not be assessed by MRI. In order to address this critical issue, this proposal will describe efforts to implement in vivo cellular and molecular MRI to image viability of transplanted mouse ESC (mESC) and functional restoration of the injured myocardium in murine model of myocardial infarction. To realize this goal, novel MRI methods, innovative cellular and molecular technologies, and a broad array of established methodologies will be integrated for a systematic study of 3 Specific Aims: Specific Aim 1 - In vivo cellular MRI will enable precise evaluation of the viability of transplanted mESC using novel off-resonance MRI sequence. Specific Aim 2 - In vivo molecular MRI of genetically engineered cells will detect viability of transplanted mESC using MRI reporter gene and targeted contrast agent. Specific Aim 3 - Viable mESC will enhance functional restoration of the injured myocardium. This research proposal brings together multidisciplinary investigation in cardiovascular imaging and stem cell biology. This approach has enabled a convergence of innovative approaches in MRI and stem cell biology to address a critical fundamental issue: cellular viability following stem cell transplantation into the myocardium. This proposal complements the high spatial and temporal resolution of MRI with cellular and molecular techniques to amplify the sensitivity of MRI. Upon conclusion of this research, an integrated MRI platform will allow dual evaluation of cell viability and myocardial restoration. Studies have demonstrated a critical role of the infarcted myocardium in the development of congestive heart failure (CHF). The incidence of CHF is now reaching epidemic proportions. Embryonic stem cells have demonstrated the ability to restore the injured myocardium. A non-invasive method to assess the survival of transplanted cells will address a fundamental issue in this novel therapeutic option.