Changes in Circulating Stem and Progenitor Cell Numbers Following Acute Exercise in Healthy Human Subjects: a Systematic Review and Meta-analysis.

Despite of the increasing number of investigations on the effects of acute exercise on circulating stem and progenitor cell (SC) numbers, and in particular on respective subgroups, i.e. endothelial (ESC), hematopoietic (HSC), and mesenchymal (MSC) stem and progenitor cells, a consensus regarding mechanisms and extent of these effects is still missing. The aim of this meta-analysis was to systematically evaluate the overall-effects of acute exercise on the different SC-subgroups and investigate possible subject- and intervention-dependent factors affecting the extent of SC-mobilization in healthy humans. Trials assessing SC numbers before and at least one timepoint after acute exercise, were identified in a systematic computerized search. Compared to baseline, numbers were significantly increased for early and non-specified SCs (enSCs) until up to 0.5 h after exercise (0-5 min: +0.64 [Standardized difference in means], p < 0.001; 6-20 min: +0.42, p < 0.001; 0.5 h: +0.29, p = 0.049), for ESCs until 12-48 h after exercise (0-5 min: +0.66, p < 0.001; 6-20 min: +0.43 p < 0.001; 0.5 h: +0.43, p = 0.002; 1 h: +0.58, p = 0.001; 2 h: +0.50, p = 0.002; 3-8 h: +0.70, p < 0.001; 12-48 h: +0.38, p = 0.003) and for HSCs at 0-5 min (+ 0.47, p < 0.001) and at 3 h after exercise (+ 0.68, p < 0.001). Sex, intensity and duration of the intervention had generally no influence. The extent and kinetics of the exercise-induced mobilization of SCs differ between SC-subpopulations. However, also definitions of SC-subpopulations are non-uniform. Therefore, finding a consensus with a clear definition of cell surface markers defining ESCs, HSCs and MSCs is a first prerequisite for understanding this important topic.

Acute Exercise-Induced Circulating Haematopoietic Stem and Progenitor Cells in Cardiac Patients - A Case Series.

BACKGROUND: Exercise-induced circulating haematopoietic stem and progenitor cell (HPC) number has been discussed in the context of regeneration in heart disease patients. OBJECTIVE: The aim of this pilot study was to compare the effect of different exercise protocols usually applied in cardiac rehabilitation on the number of acute, exercise-induced HPCs, related to potential mediators, e.g. biomarkers of sympathetic and oxidative stress, and inflammation. METHODS: This is a case series comprising seven patients suffering from coronary heart disease (CHD) undertaken at the Center for Ambulant Cardiac Rehabilitation. Patients (n=6) performed two exercise modes (constant-load, CLE; high-intensity interval, HIIE) in randomised order. Venous blood was drawn before and immediately after each test to assess CD34+/CD45+ HPC number by flow cytometry and biomarkers in blood plasma. The primary outcome was the change in HPC number, the secondary outcomes were changes in sympathetic/oxidative stress and markers of inflammation. RESULTS: Both exercise modes resulted in a non-significant increase in HPC number after exercise, even when the results of both tests were combined. Overall, free norepinephrine increased significantly and was positively related to exercise-induced HPC number (r=0.70, p<0.05). Markers of sympathetic activation (fNE), oxidative stress (myeloperoxidase) and inflammation (interleukin-6) significantly increased after CLE and HIIE with no difference between tests. CONCLUSIONS: Interestingly, acute CLE and HIIE did not stimulate significant HPC mobilisation in CHD, although both exercise modes elevated circulating concentrations of sympathetic activation. Haematopoietic stem and progenitor cell mobilisation could be blunted due to disease-related bone-marrow exhaustion.

Myocardial infarction does not affect circulating haematopoietic stem and progenitor cell self-renewal ability in a rat model.

NEW FINDINGS: What is the central question of this study? Although peripheral blood haematopoietic stem and progenitor cells are potentially important in regeneration after acute myocardial infarction, their self-renewal ability in the post-acute phase has not yet been addressed. What is the main finding and its importance? In rat peripheral blood, we show that myocardial infarction does not negatively affect circulating haematopoietic stem and progenitor cell self-renewal ability 2 weeks after acute infarction, which suggests a constant regenerative potential in the myocardial infarction post-acute phase. Given the importance of peripheral blood haematopoietic stem and progenitor cells (HPCs) in post-acute regeneration after acute myocardial infarction (MI), the aim of the present study was to investigate the number and secondary replating capacity/self-renewal ability of HPCs in peripheral blood before and 2 weeks after MI. In female Lewis inbred rats (n = 9), MI was induced by ligation of the left coronary artery, and another nine underwent sham surgery, without ligation, for control purposes. Myocardial infarction was confirmed by troponin I concentrations 24 h after surgery. Peripheral blood was withdrawn and fractional shortening and ejection fraction of the left ventricle were assessed before (day 0) and 14 days after MI or sham surgery (day 14). After mononuclear cell isolation, primary and secondary functional colony-forming unit granulocyte-macrophage (CFU-GM) assays were performed in order to detect the kinetics of functional HPC colony counts and cell self-renewal ability in vitro. The CFU-GM counts and cell self-renewal ability remained unchanged (P > 0.05) in both groups at day 14, without interaction between groups. In the intervention group, higher day 0 CFU-GM counts showed a relationship to lower fractional shortening on day 14 (ρ = -0.82; P < 0.01). Myocardial infarction did not negatively affect circulating HPC self-renewal ability, which suggests a constant regenerative potential in the post-acute phase. A relationship of cardiac contractile function 14 days after MI with circulating CFU-GM counts on day 0 might imply functional colony count as a predictive factor for outcome after infarction.

Ultra-endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function.

Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra-endurance exercise-induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra-endurance exercise, there were significant increases in leukocytes, platelets, interleukin-6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase-9. Ultra-endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein-Barr virus was seen to be reactivated in one of seven athletes. The link between exercise-induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra-endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration.