Redefining endothelial progenitor cells using a proteomics approach
type: CreativeWork
description: The concept of endothelial progenitor cells (EPCs) has attracted considerable interest in cardiovascular research, but despite a decade of research there are still no specific markers for EPCs and results from clinical trials remain controversial. To identify membrane proteins, which could serve as potential markers for EPCs, an alternative proteomic method was adopted to obtain sufficient membrane material for proteomic analysis. Microparticles (MPs), the intact vesicles formed from the plasma membrane, were harvested from the conditioned medium of EPC cultures and their protein composition was analysed by liquid chromatography-tandem mass spectrometry. Surprisingly, the platelet-specific integrin alpha lib emerged as the most abundant integrin in EPC cultures. Subsequent experiments confirmed that the conventional methods for isolating peripheral blood-derived mononuclear cells (PBMNCs) lead to a substantial contamination with platelets. Notably, platelets readily disintegrate into platelet MPs when activated during PBMNCs isolation conditions. These platelet MPs are taken up by the PBMNCs, which acquire "endothelial" characteristics (CD31, von Willebrand factor [VWF], lectin-binding), and angiogenic properties. In a large population-based study (n =526), platelets emerged as a positive predictor for the number of colony-forming units and early outgrowth EPCs. This study provides the first evidence that the cell type consistent with current definitions of an EPC phenotype may arise from an uptake of platelet MPs by mononuclear cells resulting in a gross misinterpretation of their cellular progeny. In addition, the release of platelet MPs at sites of vascular injury may play a role in orchestrating tissue repair and contribute to the activation of an angiogenic programme in monocytes by inducing the expression of non-coding regulatory RNA, known as microRNAs, which act as translational repressers. The uptake of platelet MPs by mononuclear cells induced the release …
abstract: The concept of endothelial progenitor cells (EPCs) has attracted considerable interest in cardiovascular research, but despite a decade of research there are still no specific markers for EPCs and results from clinical trials remain controversial. To identify membrane proteins, which could serve as potential markers for EPCs, an alternative proteomic method was adopted to obtain sufficient membrane material for proteomic analysis. Microparticles (MPs), the intact vesicles formed from the plasma membrane, were harvested from the conditioned medium of EPC cultures and their protein composition was analysed by liquid chromatography-tandem mass spectrometry. Surprisingly, the platelet-specific integrin alpha lib emerged as the most abundant integrin in EPC cultures. Subsequent experiments confirmed that the conventional methods for isolating peripheral blood-derived mononuclear cells (PBMNCs) lead to a substantial contamination with platelets. Notably, platelets readily disintegrate into platelet MPs when activated during PBMNCs isolation conditions. These platelet MPs are taken up by the PBMNCs, which acquire "endothelial" characteristics (CD31, von Willebrand factor [VWF], lectin-binding), and angiogenic properties. In a large population-based study (n =526), platelets emerged as a positive predictor for the number of colony-forming units and early outgrowth EPCs. This study provides the first evidence that the cell type consistent with current definitions of an EPC phenotype may arise from an uptake of platelet MPs by mononuclear cells resulting in a gross misinterpretation of their cellular progeny. In addition, the release of platelet MPs at sites of vascular injury may play a role in orchestrating tissue repair and contribute to the activation of an angiogenic programme in monocytes by inducing the expression of non-coding regulatory RNA, known as microRNAs, which act as translational repressers. The uptake of platelet MPs by mononuclear cells induced the release …
author: Prokopi, Marianna
language: eng
date published: 2012-4-1
date modified: 2026-07-24T02:44:42Z
provider: King's College London
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: King's College London