Characterization of Two Types of Endothelial Progenitor Cells and Their Different Contributions to Neovasculogenesis

TLDR

Endothelial progenitor cells are heterogeneous and not a single cell population. The study aims to demonstrate EPC heterogeneity by isolating two distinct EPC types from the same donors. Total peripheral blood mononuclear cells were cultured sequentially to isolate early and late EPC subtypes. Early EPCs proliferate briefly and secrete more angiogenic cytokines, whereas late EPCs grow longer, express distinct surface markers, produce more nitric oxide, integrate better into endothelial monolayers, and form capillary tubes more effectively, yet both exhibit comparable in vivo vasculogenic capacity.

Abstract

Endothelial progenitor cells (EPC) in one study group is not the same as EPC in other investigators, suggesting that EPC is not a single type of cell population. In this study, we tried to demonstrate the heterogeneity of EPC.We cultured total mononuclear cells from human peripheral blood to get two types of EPC sequentially from the same donors. We called them early EPC and late EPC. Early EPC with spindle shape showed peak growth at 2 to 3 weeks and died at 4 weeks, whereas late EPC with cobblestone shape appeared late at 2 to 3 weeks, showed exponential growth at 4 to 8 weeks, and lived up to 12 weeks. Late EPC was different from early EPC in the expression of VE-cadherin, Flt-1, KDR, and CD45. Late EPC produced more nitric oxide, incorporated more readily into human umbilical vein endothelial cells monolayer, and formed capillary tube better than early EPC. Early EPC secreted angiogenic cytokines (vascular endothelial growth factor, interleukin 8) more so than late EPC during culture in vitro. Both types of EPC showed comparable in vivo vasculogenic capacity.We found two types of EPC from a source of adult peripheral blood that might have different roles in neovasculogenesis based on the identified differences.