A novel EC-specific tubulogenesis assay highlights strikingly different angiogenic properties of different EPCs: late OECs directly participate in tubulogenesis, whereas early EPCs augment angiogenesis in a paracrine fashion, with implications for optimizing cell therapies for neovascularization.

Increased blood viscosity is associated with early atherogenesis and increased cardiovascular (CV) risk. Whilst the mechanism of these associations is unclear, it may be related to increased arterial wave reflection during activities of daily living. This study aimed to test this hypothesis. Methods: Twenty patients (14 males; aged 61 ± 12 years) with polycythaemia rubra vera (n = 16) or haemachromatosis (n = 4) were studied at rest and during cycle exercise at 50% of maximal heart rate, before and after venesection (500 ml, volume replaced with saline) to elicit an acute decrease in plasma viscosity at stable blood pressure (BP). Radial tonometry was used to derive central BP and augmentation index (AIx) as a marker of arterial wave reflection. Healthy controls (n = 20) underwent the same protocol without venesection. Results: Venesection caused a significant decrease in plasma viscosity (1.46 ± 0.10-1.41 ± 0.11), protein and haemoglobin (p < 0.05 for all) in the patient group, but these parameters did not significantly change in the controls (p > 0.50 for all). Exercise AIx was significantly reduced in response to venesection (from 31 ± 11-25 ± 10%; p < 0.001), despite lack of significant change in mean arterial pressure, central or peripheral BP (p > 0.05 for all). Haemodynamics were not significantly changed in controls. Conclusions: Acute reduction in plasma viscosity lowers arterial wave reflection during light activity. Thus, the increased CV risk associated with viscosity may be related to central hypertension during daily activities.

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Abstract:The discovery, over a decade ago, of endothelial progenitor cells that are able to participate in neovascularization of adult tissue has been greeted enthusiastically because of the potential for new cell-based therapies for therapeutic angiogenesis. Since that time, an ever-growing list of candidate cells has been proposed for cardiovascular regeneration. However, to date, pre-clinical and clinical studies evaluating the therapeutic potential of various cell therapies have reported conflicting results, generating controversy. Key issues within the field of cell therapy research include a lack of uniform cellular definitions, as well as inadequate functional characterization of the role of putative stem/progenitor cells in angiogenesis. Given the mixed results of initial clinical studies, there is now a scientific imperative to understand better the vascular biology of candidate cells in order to better translate cell therapy to the bedside. This review will provide a translationally relevant overview of the biology of candidate stem/progenitor cells for therapeutic angiogenesis.