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

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.

Differentiation of Human Atrial Myocytes From Endothelial Progenitor Cell-Derived Induced Pluripotent Stem Cells

“…A final value of P≤0.05 was considered significant for all analyses. 75±6%) and CD34 (71±2.8%) [333]. In consistent with the finding that L-EPC generating precursors are derived from CD34+ CD45-cell fraction, but not to the CD34+ CD45+ hematopoietic fraction, these culture guided cell did not express hematopoietic cells specific surface antigen such as CD45 [170,333].…”

Comparative Anti-Platelet Profiling Reveals a Potent Anti-Aggregatory Effect of CD34+ Progenitor Cell-Derived Late-Outgrowth Endothelial Cells in vitro

“…Their characteristics are similar to those previously described [25,27,34,43]. In brief, MPCs are colonies which consist of multiple, thin, flat cells emanating from a central cluster of rounded cells.…”

The Role of CC-Chemokines in the Regulation of Angiogenesis

“…Under each stimulus, endothelial cells undergo increased proliferation and migration prior to assembling into tubular structures to form new blood vessels. During angiogenesis, circulating endothelial progenitor cells (EPCs) from the bone marrow promote angiogenesis in a paracrine fashion by secreting growth factors and cytokines to activate local endothelial cells for angiogenesis [38,39,40]. EPCs have also been shown to incorporate into tubules and participate in angiogenesis directly [41,42].…”