Cell Characterization and Imaging for Regenerative Therapies in Ischemic Diseases

缺血性疾病再生疗法的细胞表征和成像

• 批准号: 8288408
• 负责人: JOHN P COOKE
• 金额: $ 53.44万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-23 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8288408
• 关键词: Algorithms; Area; Biological; Bone Marrow; Bone Marrow Cells; Bone Marrow Stem Cell; CD34 gene; Cardiovascular Diseases; Cardiovascular system; Cell Therapy; Cells; Clinical; Clinical Trials; Commit; Communities; Complement; Contrast Media; Coronary; Coronary Arteriosclerosis; Cytometry; Detection; Device or Instrument Development; Devices; Disease; EFRAC; Eagles; Engraftment; Financial Support; Functional Imaging; Funding; Harvest; Heart Diseases; Human; Image; Infarction; Injection of therapeutic agent; Institutes; Ischemia; Isolated limb perfusion; Isotopes; Label; Letters; Limb structure; Magnetic Resonance Imaging; Manganese; Measurement; Measures; Methodology; Modality; Mononuclear; Myocardial; Myocardial perfusion; Natural regeneration; Patients; Perfusion; Peripheral; Peripheral Blood Mononuclear Cell; Peripheral arterial disease; Population; Preparation; Process; Protocols documentation; Randomized Clinical Trials; Research; Research Personnel; Science; Skeletal Muscle; Stem cells; Supporting Cell; Techniques; Technology; Therapeutic; Therapeutic Studies; Time; Tissues; Transition Elements; Translating; Universities; Vision; Walking; Work; Yang; adult stem cell; angiogenesis; base; cellular imaging; imaging modality; improved; in vivo; innovation; insight; molecular imaging; multimodality; new technology; novel; novel strategies; regenerative therapy; single cell analysis; small molecule; technology development

DESCRIPTION (provided by applicant): We are a collaborative and tightly knit group of investigators who wish to contribute to the CCTRN our expertise in 1) small molecules and stem cells in peripheral arterial disease (John Cooke); 2) clinical device development in stem cell delivery, coronary artery disease, and structural heart disease (William Fearon, Robert Robbins, and Alan Yeung); 3) multimodality cellular, molecular, and physiologic imaging of stem cells and ischemic cardiovascular diseases (Sanjiv Gambhir, Dwight Nishimura, Joseph Wu, and Phillip Yang); 4) bone marrow stem cell harvest and processing (Robert Negrin); and 5) stem cell characterization (Garry Nolan). We propose to contribute a novel multi-modality approach to assess stem cell engraftment employing manganese enhanced MRI (MEMRI) by Phillip Yang, and stem cell localization utilizing lndium-111 cell labeling by Joe Wu and Sam Gambhir. In addition, we will contribute innovative methodology to evaluate tissue perfusion and peri-infarct viability using magnetic resonance imaging (MRI) algorithms developed by Dwight Nishimura and Phillip Yang for peripheral and myocardial imaging, respectively. Finally, we will provide a comprehensive definition of the CD34+ mononuclear cells (MNCs) to be used in our human studies, using the paradigm-changing technology of single cell mass cytometry recently developed at Stanford (Bendall SC et al. Science 2011). This new technology provides a platform for massively multiplexed measurements of single-cell biological parameters that can finely delineate cellular subsets. We intend to correlate these subsets with clinical endpoints in our PAD and CAD research protocols, to determine what cell subsets may be most critical for any observed benefit.

描述（由申请人提供）： 我们是一个紧密协作的研究小组，希望为 CCTRN 贡献我们在 1) 外周动脉疾病中的小分子和干细胞方面的专业知识（John Cooke）； 2) 干细胞输送、冠状动脉疾病和结构性心脏病的临床设备开发（William Fearon、Robert Robbins 和 Alan Yeung）； 3) 干细胞和缺血性心血管疾病的多模态细胞、分子和生理成像（Sanjiv Gambhir、Dwight Nishimura、Joseph Wu 和 Phillip Yang）； 4) 骨髓干细胞采集和处理（Robert Negrin）； 5) 干细胞表征（Garry Nolan）。 我们建议贡献一种新颖的多模态方法来评估干细胞植入，由 Phillip Yang 使用锰增强 MRI (MEMRI)，并由 Joe Wu 和 Sam Gambhir 使用 Indium-111 细胞标记来评估干细胞定位。此外，我们将利用 Dwight Nishimura 和 Phillip Yang 分别开发的用于外周和心肌成像的磁共振成像 (MRI) 算法，贡献创新的方法来评估组织灌注和梗死周围的活力。 最后，我们将使用斯坦福大学最近开发的单细胞质量细胞计数范式改变技术（Bendall SC et al. Science 2011），提供用于人类研究的 CD34+ 单核细胞 (MNC) 的全面定义。这项新技术为单细胞生物参数的大规模多重测量提供了一个平台，可以精细地描绘细胞子集。我们打算将这些细胞亚群与我们的 PAD 和 CAD 研究方案中的临床终点相关联，以确定哪些细胞亚群对于任何观察到的益处可能最关键。