Late Outgrowth Endothelial Cells Derived From Wharton Jelly in Human Umbilical Cord Reduce Neointimal Formation After Vascular Injury

Abstract

Objectives-The number of endothelial progenitor cells (EPCs) that can be obtained from adult bone marrow and peripheral blood to treat cardiovascular diseases is limited. The goal was to examine the endothelial potential of Wharton jelly in human umbilical cord (WJC)-derived stem cells and evaluate their potential to affect neointimal formation after vascular injury. Methods and Results-Mesenchymal cells (MCs) were isolated from WJC and cultured in endothelial growth medium.Differentiation into late outgrowth endothelial cells (WJC-OECs) was demonstrated by incorporation of acetylated low-density lipoprotein and expression of the endothelial-specific markers. Transplantation of these cells into wire-injured femoral arteries in mice led to rapid reendothelialization. At 4 weeks after injury, the neointima/media area ratio was reduced and strong expression of pigment epithelium-derived factor (PEDF) compared to saline-or MC-or cord blood-OEC-treated mice. WJC-OECs-conditioned medium has an extremely strong capacity to inhibit the migration and proliferation of smooth muscle cells. The effects were inhibited by neutralizing antibody for PEDF and by siRNA silencing of PEDF. Conclusions-We

Correlation of Different NADPH Oxidase Homologues with Late Endothelial Progenitor Cell Senescence Induced by Angiotensin II: Effect of Telmisartan

“…Early and late colonies have been thus distinguished for having different proliferation potential. Compared with early EPCs, late EPCs may bring a sufficient number of endothelial cells, incorporate more readily into endothelial cell monolayer to form capillary tube and therefore contribute more to neovasculogenesis (21). In this point, anti-late EPC senescence may be a good way to lower cardiovascular risk effectively.…”

Mechanistic Insights into Arterial Repair with Mesenchymal Stromal Cells

“…These ultimately lead to excessive neointima formation and re-narrowing of the arterial lumen. Although its frequency has declined in recent years, the residual risk of restenosis after percutaneous and surgical revascularization has prompted ongoing evaluation of experimental strategies to prevent or treat its progression, including the administration of different progenitor cell types to facilitate normal arterial healing and avert aberrant, deleterious repair [3][4][5][6][7].…”

Phenotype and Differentiation Potential of Stromal Populations Obtained from Various Zones of Human Umbilical Cord: An Overview

“…The simultaneous presence of HLA-G and the lack of CD80 and CD86 suggest that Wharton's jelly-derived MSCs are particularly suitable for cell-based therapy, in accordance with the in vivo studies where the transplantation of heterologous MSCs did not elicit acute rejection [7]. Finally, contradictory findings have been obtained on the expression of CD106 [34,50], CD117 [3, 34, 41, 44-46, 53, 61], and nestin [61,62].…”

“…This latter differentiation potential may have implications for the therapy of vascular diseases. Indeed, when differentiated MSCs were transplated into wire-injured femoral arteries in mice, a quick re-endothelization and inhibition of neointimal hyperplasia were observed [50]. These effects were probably mediated by the pigment epithelium-derived growth factor (PEDF) that inhibits smooth muscle cell proliferation and possesses antioxidant properties.…”