Progenitor Cells for Arterial Repair: Incremental Advancements towards Therapeutic Reality

Abstract

Coronary revascularization remains the standard treatment for obstructive coronary artery disease and can be accomplished by either percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery. Considerable advances have rendered PCI the most common form of revascularization and improved clinical outcomes. However, numerous challenges to modern PCI remain, namely, in-stent restenosis and stent thrombosis, underscoring the importance of understanding the vessel wall response to injury to identify targets for intervention. Among recent promising discoveries, endothelial progenitor cells (EPCs) have garnered considerable interest given an increasing appreciation of their role in vascular homeostasis and their ability to promote vascular repair after stent placement. Circulating EPC numbers have been inversely correlated with cardiovascular risk, while administration of EPCs in humans has demonstrated improved clinical outcomes. Despite these encouraging results, however, advancing EPCs as a therapeutic modality has been hampered by a fundamental roadblock: what constitutes an EPC? We review current definitions and sources of EPCs as well as the proposed mechanisms of EPC-mediated vascular repair. Additionally, we discuss the current state of EPCs as therapeutic agents, focusing on endogenous augmentation and transplantation.

LncRNA WTAPP1 Promotes Migration and Angiogenesis of Endothelial Progenitor Cells via MMP1 Through MicroRNA 3120 and Akt/PI3K/Autophagy Pathways

“…In the setting of DVT, endothelial progenitor cells (EPCs), which are a type of bone marrow‐derived circulating progenitor cell in the endothelial lineage, have been reported to have the abilities to home in on and migrate to disease sites to facilitate thrombus recanalization and resolution by neovascularization, increase new blood vessel formation at the injured site, and secrete a variety of vasoactive and angiogenic factors to improve angiogenesis . Furthermore, EPCs have the capacity to protect differentiated endothelial cells from apoptosis, thereby preserving their angiogenic potential under conditions of oxidative stress . In our previous study, we demonstrated that the transplantation of normal and gene‐modified bone marrow‐derived EPCs altered the vein microenvironment and facilitated thrombus resolution in a rat model of vein thrombosis .…”

Upregulating CXCR7 Accelerates Endothelial Progenitor Cells Mediated Endothelial Reparation via Activating Akt/Keap-1/Nrf2 Signaling in Diabetes Mellitus

“…The levels of EPCs, which contributed to endothelial reparation via paracrine effect or transdifferentiating into mature endothelial cells [8], reduced signi cantly in patients with DM and other diabetes-related disorders. Transplantation of exogenous EPCs was considered as a potential method to promote endothelial reparation via elevating the circulating EPC level directly in a rabbit model [34].…”

“…However, unfavorable events after stent implantation, such as in-stent restenosis and late stent thrombosis, remain a serious clinical challenge [3,4]. A large body of evidence showed that endothelium injury caused by DM or interventional therapy contributed to these unfavorable vascular events [5][6][7][8]. Previous studies demonstrated that endothelial progenitor cells (EPCs) were vital in endothelial reparation [6][7][8][9].…”

“…A large body of evidence showed that endothelium injury caused by DM or interventional therapy contributed to these unfavorable vascular events [5][6][7][8]. Previous studies demonstrated that endothelial progenitor cells (EPCs) were vital in endothelial reparation [6][7][8][9]. However, DM impaired EPCs function and decreased the circulating EPCs level in either patients or mice with diabetes [10][11][12].…”

Rebuttal from Ryan M. Sapp and James M. Hagberg

“…; Simard et al . ), to our knowledge there is no study showing incorporation of EPCs into the pre‐existing vasculature of healthy animals as a means of endothelial repair in response to an acute bout of exercise. Assuming an increase in EPCs always reflects endothelial damage is, therefore, a flawed assumption that should be questioned considering that the currently available data on healthy individuals do not support an increase in CECs due to exercise.…”