CIRCULATING ENDOTHELIAL PROGENITOR CELL ASSAY VALIDATION FOR CLINICAL RESEARC

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。通过建立最佳采样条件、重测可靠性和检测对外源性粒细胞集落刺激因子诱导的CEP迁移的响应性，验证临床和流行病学研究中使用的各种CEP检测。 对循环内皮祖细胞（CEP）的研究已经注意到CEP频率和临床结果之间的直接相关性。然而，许多不同的方法已被用来量化CEP（和CEP功能）。关于这些检测方法用于临床和流行病学研究的有效性的信息很少。骨髓源性干细胞（BM-SCs）近年来受到广泛关注，干细胞移植的治疗潜力正在积极探索中。BM-SC也可以通过外周循环运输到远端器官以参与损伤后的修复，这一点也变得越来越清楚。在血液中发现的一种特定类型的干细胞是所谓的循环内皮祖细胞（CEP）>器官损伤和损伤导致的介质已被证明会增加BM-SC向损伤部位的运输。已经显示增加CEP运输的两种介质是血管内皮生长因子和粒细胞集落刺激因子（G-CSF）。在这两者中，目前只有G-CSF用于临床医学。G-CSF最为人所知的是在骨髓毒性治疗后重建血小板减少症患者，但也被FDA批准用于动员祖细胞进入外周血，以通过白细胞分离术收集。此外，G-CSF给药最近已被证明可以增加BM-SC向损伤组织的运输，并在动物模型中实现损伤的修复。该研究将增强我们对G-CSF动员内皮祖细胞进入人类外周循环的能力的理解。其效用是显著的：1）G-CSF施用可用作干细胞功能的体内测定，其可用于理解疾病过程; 2）G-CSF可用作用于修复受损组织的细胞疗法的替代方案。拟议的研究将验证循环干细胞流行率和功能的测定。这些数据反过来将成为未来研究CEP和各种疾病过程的基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Validation of various CEP assays for use in clinical and epidemiologic studies by establishing optimal sampling conditions, the test-retest realiability and assay responsiveness to exogenous granulocyte colony stimulating factor-induced CEP mobiliation. Studies examing circulating endothelial progenitor cells (CEPs) have noted a direct correlation between CEP frequency and clinical outcomes. However, a number of different methodologies have been employed to quantify CEPs (and CEP function). Little information is available concerning the validity of these assays for use in clinical and epidemiologic research. Bone marrow-derived stem cells (BM-SCs) have garnered much attention recently and the therapeutic potential stem cell transplantation is actively being explored. It is also becoming clear that BM-SCs may also traffic through the peripheral circulation en route to distal organs to participate in repair after injury. One specific type of stem cell found in the blood is the so-called Circulating Endothelial Progenitor cell (CEP)> Organ injury and mediators produced as a result of injury have been shown to increase the trafficking of BM-SC to the site of damage. Two mediators that have been shown to increase the trafficking of CEPs are vascular endothelial growth factor and granulocyte-colony stimulating factor (G-CSF). Of these two, only G-CSF is currently used in clinical medicine. G-CSF is best known for reconstituting neutropenic patients after myelotoxic therapy but is also FDA-approved for the mobilization of progenitor cells into the peripheral blood for collection by leukapheresis. Additionally, G-CSF administration has recently been shown to augment BM-SC trafficking to injured tissue and effect repair of damage in animal models. The study will enhance our understanding of the ability of G-CSF to mobilize endothelial progenitors into the peripheral circulation in humans. The utility of this is significant: 1) G-CSF administration may serve as an in vivo assay of stem cell function which may be useful in understanding disease processes; 2) G-CSF may serve as an alternative to cell therapy for the repair of injured tissues. The proposed studies will validate assays of circulating stem cell prevalence and function. This data will in turn form the basis for future studies of CEPs and a variety of disease processes.