Cell Characterization and Imaging for Regenerative Therapies in Ischemic Diseases

描述（由申请人提供）： 我们是一个紧密合作的研究小组，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（约翰库克）; 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，and 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，德怀特Nishimura，Joseph Wu和菲利普杨）; 4）骨髓干细胞收获和处理（Robert Negrin）;和5）干细胞表征（Garry Nolan）。 我们提出了一种新的多模态方法来评估干细胞植入，采用锰增强MRI（MEMRI）的菲利普杨，和干细胞定位利用铟-111细胞标记的乔吴和山姆Gambhir。此外，我们将贡献创新的方法来评估组织灌注和梗死周围的活力，使用磁共振成像（MRI）算法开发的德怀特西村和菲利普杨外周和心肌成像，分别。 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的范式改变技术（Bendall SC et al. Science 2011），提供用于人体研究的CD 34+单核细胞（MNC）的全面定义。这项新技术为单细胞生物学参数的大规模多路测量提供了一个平台，可以精细地描绘细胞亚群。我们打算将这些亚群与我们的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可能对任何观察到的益处最关键。

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.