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.
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