Endothelial Progenitor Cells in Neurovascular Disorders-A Comprehensive Overview of the Current State of Knowledge

Abstract

Endothelial progenitor cells (EPCs) are a population of cells that circulate in the blood looking for areas of endothelial or vascular injury in order to repair them. Endothelial dysfunction is an important component of disorders with neurovascular involvement. Thus, the subject of involvement of EPCs in such conditions has been gaining increasing scientific interest in recent years. Overall, decreased levels of EPCs are associated with worse disease outcome. Moreover, their functionalities appear to decline with severity of disease. These findings inspired the application of EPCs as therapeutic targets and agents. So far, EPCs appear safe and promising based on the results of pre-clinical studies conducted on their use in the treatment of Alzheimer's disease and ischemic stroke. In the case of the latter, human clinical trials have recently started to be performed in this subject and provided optimistic results thus far. Whereas in the case of migraine, existing findings pave the way for testing EPCs in in vitro studies. This review aims to thoroughly summarize current knowledge on the role EPCs in four disorders with neurovascular involvement, which are Alzheimer's disease, cerebral small vessel disease, ischemic stroke and migraine, with a particular focus on the potential practical use of these cells as a treatment remedy.

Keywords: Alzheimer disease; endothelial dysfunction; endothelial progenitor cells; ischemic stroke; migraine.

Figure 1

Characteristics of endothelial progenitor cells. Abbreviations: CACs–circulatory angiogenic cells; CFU-ECs–colony-forming unit endothelial cells; ECFCs–endothelial colony-forming cells; EPCs–endothelial progenitor cells; IGF-1–insulin-like growth factor 1; OECs–outgrowth endothelial cells; SDF-1α–stromal cell-derived factor-1α; VE-cadherin–vascular endothelial cadherin; VEGF–vascular endothelial growth factor; VEGFR-2–vascular endothelial growth factor receptor-2; vWF–von Willebrand factor. Image created with biorender.com; accessed on 22 September 2022.