Cellular and Molecular MRI of Stem Cell Viability

描述（由申请人提供）：对移植细胞在受损心肌中的植入进行成像的体内方法将能够精确评价细胞治疗。植入是一个复杂的级联生物过程，包括细胞存活和受体组织的功能恢复。虽然MRI已成为追踪离体标记细胞的主要方式之一，但MRI无法评估细胞活力的确切信息。为了解决这一关键问题，本提案将描述努力实现在体内的细胞和分子MRI图像移植的小鼠ESC（mESC）的生存能力和功能恢复受损的心肌在小鼠心肌梗死模型。为了实现这一目标，新的MRI方法，创新的细胞和分子技术，以及广泛的一系列已建立的方法将被整合用于3个特定目标的系统研究：特定目标1 -体内细胞MRI将使用新的非共振MRI序列精确评估移植mESC的活力。具体目标2 -基因工程细胞的体内分子MRI将使用MRI报告基因和靶向造影剂检测移植的mESC的活力。具体目标3 -活的mESC将增强受损心肌的功能恢复。这项研究计划汇集了心血管成像和干细胞生物学的多学科研究。这种方法使MRI和干细胞生物学的创新方法能够融合，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，以放大MRI的灵敏度。在这项研究结束后，一个集成的MRI平台将允许细胞活力和心肌恢复的双重评价。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。CHF的发病率现已达到流行病的比例。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.