Proliferative potential and angiogenic characteristics of blood outgrowth endothelial cells derived from middle-aged and older adults.

Abstract

Objectives: Autologous blood outgrowth endothelial cells (BOECs) have been proposed to induce therapeutic angiogenesis for treating cardiovascular diseases (CVDs). The aim of the present study was to investigate the proliferative potential and angiogenic characteristics of BOECs among middle-aged and older adults, the population particularly susceptible to CVDs.

Methods: BOECs were isolated from 48 peripheral blood samples of subjects aged 56 ± 4 years. The cells were then distinguished based on their proliferative abilities, and their phenotype, tube formation capacity, and migratory activity were compared using immunofluorescence staining, flow cytometry, tube formation assay, and wound healing assay, respectively. Correlations between demographic, clinical, and dietary parameters with the number of BOECs were also assessed.

Results: A total of 132 BOEC colonies with different proliferative potentials were obtained, including colonies lost proliferative ability before passage 3 (named LPA), stopped proliferating during passage 3-8 (HPA (3-8)), and proliferated after passage 8 (HPA (> 8)). LPA cells appeared later and displayed abnormal morphology, while HPA (3-8) cells exhibited alterations in von Willebrand factor morphology and lower KDR expression. HPA (> 8) cells obtained higher branching intervals and individual cell migration velocity compared with those of HPA (3-8) cells. Correlation analysis showed that the number of both LPA and HPA colonies were positively associated with several CVD risk factors. Additionally, the number of LPA colonies was positively associated with servings of meats and alternatives, fruits, fruits and vegetables, as well as the protein intake.

Conclusions: Our findings provide evidence that the middle-aged and older populations possess BOECs with different proliferative and angiogenic potentials, exhibiting distinctions in cell morphology, appearance dates, VWF morphology, and KDR expression. Strikingly, a higher number of BOECs is likely associated with an increased risk of CVDs, while the number of BOECs with low proliferative ability may be regulated by diet.