Exploring Endothelial Colony-Forming Cells to Better Understand the Pathophysiology of Disease: An Updated Review

Abstract

Endothelial cell (EC) dysfunction has been implicated in a variety of pathological conditions. The collection of ECs from patients is typically conducted postmortem or through invasive procedures, such as surgery and interventional procedures, hampering efforts to clarify the role of ECs in disease onset and progression. In contrast, endothelial colony-forming cells (ECFCs), also termed late endothelial progenitor cells, late outgrowth endothelial cells, blood outgrowth endothelial cells, or endothelial outgrowth cells, are obtained in a minimally invasive manner, namely, by the culture of human peripheral blood mononuclear cells in endothelial growth medium. ECFCs resemble mature ECs phenotypically, genetically, and functionally, making them excellent surrogates for ECs. Numerous studies have been performed that examined ECFC function in conditions such as coronary artery disease, diabetes mellitus, hereditary hemorrhagic telangiectasia, congenital bicuspid aortic valve disease, pulmonary arterial hypertension, venous thromboembolic disease, and von Willebrand disease. Here, we provide an updated review of studies using ECFCs that were performed to better understand the pathophysiology of disease. We also discuss the potential of ECFCs as disease biomarkers and the standardized methods to culture, quantify, and evaluate ECFCs and suggest the future direction of research in this field.

Mitochondrial Dysfunction in Endothelial Progenitor Cells: Unraveling Insights from Vascular Endothelial Cells

“…ECFCs of type II diabetic patients show increased mitochondrial fragmentation and dysregulation of proteins involved in mitochondrial dynamics [286]. Furthermore, and as mentioned before, diabetic ECFCs are functionally compromised, with reduced proliferation, tube formation, and weakened survival capacities [25,257]. However, upregulated expression of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor involved in redox balance, seems to counteract these DM-induced effects in ECFCs from diabetic patients.…”

“…Moreover, EPCs from diabetic patients differ regarding in vitro cultivation. For instance, isolated ECFCs from T2DM patients show impaired colony outgrowth, less tube formation, decreased proliferation, migration, and impaired in vivo neovascularization (the latter was shown in an animal model) [25,257]. Notably, improved glycemic control also positively impacts EPC numbers and improves the function of differentiated ECFCs [256,258].…”

Philadelphia chromosome-negative myeloproliferative chronic neoplasms: is clonal hematopoiesis the main determinant of autoimmune and cardio-vascular manifestations?

“…Focusing on vessels, endothelial cells (ECs) carrying the JAK2V617F mutation have been detected in patients with MPNs. Mesodermal pluripotent stem cells, indeed, have the capacity to differentiate into both hematopoietic and endothelial lineages ( 86 , 87 ). In instances where vascular endothelial integrity is compromised, re-endothelialization can occur through the outgrowth of neighboring intact endothelium or by repopulating EC progenitors.…”

Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia

“…The early EPC phenotype represented by the expression of CD133, among others, showed better proliferative activity and greater distribution of primitive progenitors than other studied populations [ 30 ]. Early EPCs, also known as myeloid angiogenic cells (MACs), promote angiogenesis in a paracrine fashion, whereas late EPCs, also called endothelial colony-forming cells (ECFC), participate more directly in the formation of new vasculature [ 31 , 32 ]. An enriched population of early progenitors can be obtained prior to cultivation by magnetic cell sorting based on positive selection of CD133 + [ 33 ].…”