Cellular and Molecular MRI of Stem Cell Viability

描述（由申请人提供）：一种对移植细胞植入损伤心肌的体内成像方法将使细胞治疗的精确评估成为可能。移植是一个复杂的级联生物学过程，包括细胞存活和受体组织的功能恢复。尽管MRI已成为跟踪离体标记细胞的主要方式之一，但关于细胞活力的明确信息不能通过MRI进行评估。为了解决这一关键问题，本提案将描述在小鼠心肌梗死模型中实施体内细胞和分子MRI来成像移植小鼠ESC （mESC）的活力和损伤心肌功能恢复的努力。为了实现这一目标，新的MRI方法、创新的细胞和分子技术以及广泛的既定方法将被整合到3个特定目标的系统研究中：特定目标1 -体内细胞MRI将能够使用新的非共振MRI序列精确评估移植的mESC的生存能力。特异性目的2 -基因工程细胞的体内分子MRI将利用MRI报告基因和靶向造影剂检测移植mESC的活力。特异性目的3 -有活力的mESC可促进损伤心肌的功能恢复。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。这种方法使MRI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：干细胞移植到心肌后的细胞活力。这一建议补充了高空间和时间分辨率的MRI与细胞和分子技术，以扩大MRI的敏感性。在这项研究的结论，一个集成的MRI平台将允许双重评估细胞活力和心肌恢复。研究表明，心肌梗死在充血性心力衰竭（CHF）的发展中起着关键作用。目前，瑞士法郎的发病率已达到流行病的程度。胚胎干细胞已被证明具有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种新型治疗选择的一个基本问题。

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.