Abstract

Blood outgrowth smooth muscle cells (BO-SMCs) offer the means to study vascular cells without the requirement for surgery providing opportunities for drug discovery, tissue engineering, and personalized medicine. However, little is known about these cells which meant that their therapeutic potential remains unexplored. Our objective was to investigate for the first time the ability of BO-SMCs and vessel-derived smooth muscle cells to sense the thromboxane mimetic U46619 by measuring intracellular calcium elevation and contraction. U46619 (10–6 M) increased cytosolic calcium in BO-SMCs and vascular smooth muscle cells (VSMCs) but not in fibroblasts. Increased calcium signal peaked between 10 and 20 s after U46619 in both smooth muscle cell types. Importantly, U46619 (10–9 to 10–6 M) induced concentration-dependent contractions of both BO-SMCs and VSMCs but not in fibroblasts. In summary, we show that functional responses of BO-SMCs are in line with VSMCs providing critical evidence of their application in biomedical research.

Highlights

  • Blood vessels consist of smooth muscle lined by endothelial cells

  • For the first time, we have investigated the ability of blood outgrowth smooth muscle cells (BO-smooth muscle cells (SMCs)) to sense a physiologically relevant stimulus, the thromboxane mimetic U46619, resulting in intracellular calcium elevation and contraction, and have directly compared responses to those obtained in vessel-derived SMCs (VSMCs) and fibroblasts

  • Upon stimulation with U46619, organized changes of cytosolic calcium were observed in BOSMCs and vascular smooth muscle cells (VSMCs) but not fibroblasts

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Summary

Introduction

Vascular cells can only be obtained postsurgery or after death. Both cell types can be grown out and differentiated from human blood (Simper et al, 2002; Sugiyama et al, 2006; Ahmetaj-Shala et al, 2020) in the form of blood outgrowth endothelial cells [BOECs; known as endothelial colony forming cells (ECFC); Paschalaki and Randi, 2018] and blood outgrowth smooth muscle cells (BO-SMCs; Simper et al, 2002), providing an accessible cell source for studying vascular biology in healthy individuals or patients with disease. The origins of endothelial and smooth muscle progenitor cells that form BOECs and BO-SMCs still remain unclear. For BO-SMCs, lineage tracing has shown that smooth muscle progenitor cells

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