Cellular and Molecular MRI of Stem Cell Viability

干细胞活力的细胞和分子 MRI

• 批准号: 7190797
• 负责人: PHILLIP CHUNG-MING YANG
• 金额: $ 14.91万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-05 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7190797
• 关键词: Acute; Acute myocardial infarction; Address; Admission activity; American; Biological Process; Cardiac Myocytes; Cardiovascular system; Case Study; Cause of Death; Cell Survival; Cell Therapy; Cell Transplants; Cells; Cellular biology; Cessation of life; Classification; Complement; Complex; Congestive; Congestive Heart Failure; Contrast Media; Coronary Arteriosclerosis; Development; Disease; Engraftment; Epidemic; Evaluation; Facility Construction Funding Category; Gene Targeting; Goals; Heart failure; Hospitals; Image; In Vitro; Incidence; Infarction; Invasive; Investigation; Label; Magnetic Resonance Imaging; Medical; Methodology; Methods; Modality; Modeling; Molecular; Morbidity - disease rate; Mus; Myocardial; Myocardial Infarction; Myocardium; Numbers; Operative Surgical Procedures; Patients; Population; Process; Public Health; Reporter; Reporter Genes; Research; Research Proposals; Resolution; Role; Stem cell transplant; Stem cells; Techniques; Technology; Tissues; Today; Transplantation; Treatment Efficacy; United States; Validation; cardiovascular imaging; embryonic stem cell; functional restoration; genetically modified cells; improved; in vivo; injured; innovation; interdisciplinary approach; mortality; multidisciplinary; novel; novel therapeutics; restoration

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.

描述（由申请人提供）：一种体内方法，用于对受伤的心肌中移植细胞的植入植入，将实现细胞疗法的精确评估。植入是一系列复杂的生物过程级联，包括细胞存活和受体组织的功能恢复。尽管MRI已成为跟踪过体标记细胞的主要模式之一，但无法通过MRI评估细胞活力的明确信息。为了解决这个关键问题，该提案将描述实施体内细胞和分子MRI的努力，以形象移植小鼠ESC（MESC）的生存能力以及在心肌梗死的鼠模型中受伤的心肌的功能恢复。为了实现这一目标，将将新颖的MRI方法，创新的细胞和分子技术以及一系列已建立的方法集成到3个具体目标的系统研究中：特定的目标1-体内细胞MRI将促进使用新型MESC使用新型MESC使用新颖的非差异MRI序列进行精确评估。特定的目标2-基因工程细胞的体内分子MRI将使用MRI报告基因和靶向对比剂检测移植MESC的生存力。特定的目标3-可行的MESC将增强受伤心肌的功能恢复。该研究建议汇集了心血管成像和干细胞生物学中的多学科研究。这种方法使MRI和干细胞生物学中创新方法的融合能够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。该提案通过细胞和分子技术补充了MRI的高空间和时间分辨率，以扩大MRI的敏感性。在本研究结束后，集成的MRI平台将允许对细胞活力和心肌恢复双重评估。研究表明，梗塞心肌在充血性心力衰竭（CHF）的发展中起着关键作用。 CHF的发生率现在达到流行比例。胚胎干细胞已证明能够恢复受伤的心肌。评估移植细胞存活的一种非侵入性方法将解决这种新型治疗选择中的基本问题。