Cell Characterization and Imaging for Regenerative Therapies in Ischemic Diseases

描述(由申请人提供)： 我们是一群协作、紧密的研究人员，希望在以下方面为CCTRN做出贡献：1)外周动脉疾病中的小分子和干细胞(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)干细胞特性(Garry Nolan)。 我们建议提供一种新的多模式方法来评估干细胞植入，使用Phillip Yang的锰增强磁共振成像(MEMRI)，以及使用Joe Wu和Sam Gambhir的In-111细胞标记进行干细胞定位。此外，我们将使用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，为评估组织灌注和梗死周围生存能力提供创新的方法。 最后，我们将使用斯坦福大学最近开发的改变范式的单细胞质量细胞术技术(Bendall SC等人)，为我们的人类研究中使用的CD34+单核细胞(MNC)提供一个全面的定义。科学2011年)。这项新技术为单细胞生物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。我们打算在我们的PAD和CAD研究方案中将这些细胞亚群与临床终点相关联，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.