Aerobic exercise in humans mobilizes HSCs in an intensity-dependent manner

Abstract

Hematopoietic stem and progenitor cells are necessary to maintain, repair, and reconstitute the hematopoietic blood cell system. Mobilization of these cells from bone marrow to blood can be greatly increased under certain conditions, one such being exercise. The purpose of this study was to identify the importance of exercise intensity in hematopoietic mobilization, to better understand the mobilization kinetics postexercise, and to determine if exercise is capable of mobilizing several specific populations of hematopoietic cells that have clinical relevance in a transplant setting. Healthy individuals were exercised on a cycle ergometer at 70% of their peak work rate (WR_peak) until volitional fatigue and at 30% of their WR_peak work matched to the 70% WR_peak bout. Blood was collected before, immediately post, and 10, 30, and 60 min postexercise. Total blood cells, hematocrit, and mononuclear cells isolated by density gradient centrifugation were counted. Specific populations of hematopoietic stem cells were analyzed by flow cytometry. Mononuclear cells, CD34⁺, CD34⁺/CD38^-, CD34⁺/CD110⁺, CD3^-/CD16⁺/CD56⁺, CD11c⁺/CD123^-, and CD11c^-/CD123⁺ cells per millilter of blood increased postexercise. Overall, the 70% WR_peak exercise group showed greater mobilization immediately postexercise, while there was no observable increase in mobilization in the work matched 30% WR_peak exercise group. Mobilization of specific populations of hematopoietic cells mirrored changes in the general mobilization of mononuclear cells, suggesting that exercise serves as a nonspecific mobilization stimulus. Evidently, higher intensity exercise is capable of mobilizing hematopoietic cells to a large extent and immediately postexercise is an ideal time point for their collection.

New & noteworthy: Here we demonstrate for the first time that mobilization of hematopoietic stem cells (HSCs) through exercise is intensity dependent, with the greatest mobilization occurring immediately after high-intensity exercise. As well, we show that exercise is a general stimulus for mobilization: increases in specific HSC populations are reliant on general mononuclear cell mobilization. Finally, we demonstrate no differences in mobilization between groups with different aerobic fitness.

Keywords: bone marrow transplant; exercise; flow cytometry; hematopoietic stem cells.

Fig. 1.

Mononuclear cells. Mononuclear cell counts, as isolated through density gradient centrifugation, expressed per milliliters of blood for the 70% WR_peak and 30% WR_peak exercise sessions across the time course (where WR_peak is peak work rate). *P < 0.05, between groups and from before (Pre) exercise with respect to time.

Fig. 2.

CD34⁺ cells per milliliters blood. CD34⁺ cell counts, analyzed with flow cytometry, expressed per milliliters of blood for the 70% WR_peak and 30% WR_peak exercise sessions across the time course. *P < 0.05, between groups and from Pre exercise with respect to time.

Fig. 3.

Specific hematopoietic stem cell (HSC) populations. Five different blood cell populations, analyzed by flow cytometry, known to positively correlate with successful outcomes post blood cell graft. A: CD34⁺/CD38⁻. B: CD3⁻/CD(16+56)⁺. C: CD4⁺/CD8⁺ ratio. D: CD34⁺/CD41⁺. E: CD34⁺/CD110⁺. Each expressed as positive cells per milliliters of blood for the 70% WR_peak and 30% WR_peak exercise sessions, across the time course. *P < 0.05,between groups and from Pre exercise with respect to time.

Fig. 4.

Dendritic cell populations. Two dendritic cell populations, analyzed by flow cytometry, known to positively correlate with successful outcomes post blood cell graft. A: CD11c⁺/CD123⁻. B: CD11c⁻/CD123⁺. Each expressed as positive cells per milliliters of blood for the 70% WR_peak and 30% WR_peak exercise sessions, across the time course. *P < 0.05, between groups and from Pre exercise with respect to time.

Fig. 5.

Long-term culture initiating cell frequency (LTC-IC), expressed as number of cells per milliliters blood, Pre and immediately Post exercise for the 70% WR_peak and 30% WR_peak exercise sessions. *P < 0.05, between groups and between Pre and immediately after (Post) exercise with respect to time.

Fig. 6.

Fitness comparison. A comparison between mononuclear cell counts, as isolated by density gradient centrifugation, expressed per milliliters of blood for the 70% WR_peak and 30% WR_peak exercise sessions, including the two fitness subgroups, across the time course. *P < 0.05, within fitness level subgroups for intensity, but no differences were detected between the 2 fitness subgroups.