Distinct angiogenesis roles and surface markers of early and late endothelial progenitor cells revealed by functional group analyses

Cheng-Chung Cheng,Shu-Meng Cheng,Yu-Neng Chueh,Hsei-Wei Wang,Tse-Shun Huang,Shing-Jyh Chang,Po-Hsun Huang,Tsung-Neng Tsai,Jaw-Wen Chen

doi:10.1186/1471-2164-14-182

Abstract

BackgroundEndothelial progenitor cells (EPCs) play a fundamental role in post-natal vascular repair. Currently EPCs are defined as either early and late EPCs based on their biological properties and their time of appearance during in vitro culture. EPCs are rare and therefore optimizing isolation and culture is required before they can be applied as part of clinical therapies.ResultsWe compared the gene profiles of early/late EPCs to their ancestors CD133+ or CD34+ stem cells and to matured endothelial cells pinpointing novel biomarkers and stemness genes. Late EPCs were enriched with proliferation and angiogenesis genes, participating in endothelial tubulogenesis and hence neovascularization. Early EPCs expressed abundant inflammatory cytokines and paracrine angiogenic factors, thereby promoting angiogenesis in a paracrine manner. Transcription factors involved in EPC stemness were pinpointed in early EPCs (MAF/MAFB) and in late EPCs (GATA6/IRF6).ConclusionsThe detailed mRNA expression profiles and functional module analysis for different EPCs will help the development of novel therapeutic modalities targeting cardiovascular disease, tumor angiogenesis and various ischemia-related diseases.

Highlights

Endothelial progenitor cells (EPCs) play a fundamental role in post-natal vascular repair
Late EPCs with a cobblestone-like morphology similar to mature endothelial cells grew to confluence at days 14–21
The majority of cells that were late EPCs and HUVECs expressed CD31, and kinase insert domain receptor (KDR) endothelial markers, while hematological marker CD45 was present on Early EPCs (eEPCs) (Figure 1A)

Summary

Introduction

Endothelial progenitor cells (EPCs) play a fundamental role in post-natal vascular repair. EPCs are defined as either early and late EPCs based on their biological properties and their time of appearance during in vitro culture. EPCs are rare and optimizing isolation and culture is required before they can be applied as part of clinical therapies. Post-natal neoangiogenesis relies largely on circulating endothelial progenitor cells (EPCs) [1]. The regulation of angiogenesis depends on the number of circulating EPC and on their activities [1]. Current EPC definitions are based predominantly on phenotypes and biological properties. EPCs (eEPCs) appear early (

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