CD34+ hematopoietic stem cells are mobilized with exercise independently of beta-2 adrenergic receptor signaling

Abstract

A single exercise bout mobilizes CD34+ hematopoietic stem cells (HSCs) to the bloodstream, potentially serving as an economical adjuvant to boost the collection of HSCs from stem cell transplant donors. The mechanisms responsible for HSC mobilization with exercise are unknown but are likely due to hemodynamic perturbations and/or beta-2 adrenergic receptor signaling. The aim of this study was to delineate the effects of beta-2 adrenergic receptor signaling from hemodynamic perturbations on the mobilization of CD34+ HSCs with exercise. In a randomized double-blind crossover design,10 healthy men completed 30-min of high-intensity steady state cycling exercise after ingesting (i) a selective beta1-adrenergic receptor antagonist (bisoprolol); (ii) a non-selective beta-1 + beta-2 adrenergic receptor antagonist (nadolol); or (iii) placebo. CD34 + HSCs were enumerated in blood before and after exercise by flow cytometry. Relative to placebo, nadolol and bisoprolol reduced hemodynamic perturbations with exercise (as determined by exercising heart rate and blood pressure) to comparable levels. Exercise mobilized CD34+ HSCs in all three trials, but the relative mobilization was markedly lower and comparable between the nadolol and bisoprolol trials (placebo: 118 ± 68%, bisoprolol: 67 ± 33%, and nadolol: 57 ± 38%). We conclude that the mobilization of CD34+ HSCs with exercise is not dependent on beta-2 adrenergic receptor signaling and is likely due to increased hemodynamic perturbations within the vasculature and/or beta-1 adrenergic receptor activation.