Quantum Dot-Based Profile Imaging of EPC Subpopulations and Effect on Retinal NV

描述（由申请人提供）：内皮祖细胞（EPC）是许多疾病（如动脉粥样硬化和癌症）的新生血管成分的重要参与者。目前对内皮祖细胞的研究已经根据在细胞表面上表达的抗原的子集鉴定了表达不同表型的几种不同亚群。此外，有证据表明疾病中祖细胞亚群的功能不同。特别地，EPCs向新血管形成部位的募集可能是亚群特异性现象。因此，基于抗原定义的亚群阐明EPC功能可能有助于开发旨在抑制或增强EPC功能的定制的高效治疗剂，以及更详细地了解EPC在许多疾病发病机制中的作用。目前还没有开发出描述循环中多种细胞亚型活性的体内成像工具。我们试图评估新生血管的能力，各种内皮祖细胞亚群使用一个既定的早产儿视网膜病变的动物模型，结合实时，多光谱，量子点nanocondialbased成像系统，使一个连续的，非侵入性的看法视网膜循环。我们的努力是宾夕法尼亚大学实验室在早产儿视网膜病变的发病机制和治疗干预措施的发展方面的专业知识的产物，以及最近分离和培养不同的EPC亚群的努力。Haselton实验室最近开发了一种多光谱实时成像工具，用于研究糖尿病大鼠模型中多种细胞和生物分子炎症介质。我们的方法将使用具有不同分子表达谱的细胞亚群的量子点编码来探测视网膜循环中的EPC活性，从而首次提供用于阐明细胞亚型背景下EPC功能的高通量模板，以及以高空间和时间分辨率实时评估针对这些亚型的治疗干预措施。

DESCRIPTION (provided by applicant): Endothelial progenitor cells (EPCs) are highly significant participants in the neovascular component of a host of diseases, such as atherosclerosis and cancer. Current research on endothelial progenitor cells has identified several different subpopulations expressing varying phenotypes according to the subset of antigens that are expressed on the cells' surface. Furthermore, evidence is suggestive of varying functions among progenitor cell subpopulations in disease. Specifically, the recruitment of EPCs to sites of neovascularization may be a subpopulation-specific phenomenon. Thus, an elucidation of EPC function based on antigenically-defined subpopulations may facilitate the development of customized, high-efficacy therapeutics aimed at the inhibition or enhancement of EPC function, as well as a more detailed understanding of the role of EPCs in the pathogenesis of numerous diseases. Current in vivo imaging tools to profile the activities of multiple cell subtypes in the circulation have not been developed. We seek to assess the neovascular capacity of various endothelial progenitor subsets using an established animal model of retinopathy of prematurity, in conjunction with a real-time, multispectral, quantum dot nanocrystalbased imaging system which enables a continuous, non-invasive view of the retinal circulation. Our effort is an outgrowth of the Penn laboratory's expertise in the pathogenesis and development of therapeutic interventions of retinopathy of prematurity, as well as the recent effort to isolate and culture distinct EPC subsets. The Haselton laboratory has recently developed a multispectral, real-time imaging tool for the study of multiple cellular and biomolecular mediators of inflammation in a rat model of diabetes. Our approach will use the quantum dot coding of cell subpopulations with varying molecular expression profiles to probe EPC activity in the retinal circulation, thus affording, for the first time, a high-throughput template for the elucidation of EPC function in the context of cell subtypes, as well as the evaluation of therapeutic interventions directed towards these subtypes, in real-time at high spatial and temporal resolution.