J Appl Physiol (1985). 2016 Jan 7:jap.00925.2015. doi: 10.1152/japplphysiol.00925.2015. [Epub ahead of print]

Acute Exercise Mobilizes Hematopoietic Stem and Progenitor Cells and Alters the Mesenchymal Stromal CellSecretome.

Emmons R¹, Niemiro G¹, Owolabi O¹, De Lisio M².

Abstract

Transplantation of hematopoietic stem and progenitor cells (HSPC), collected from peripheral blood, is the primary treatment for many hematological malignancies; however, variable collection efficacy with current protocols merits further examination into factors responsible for HSPC mobilization. HSPCs primarily reside within the bone marrow and are regulated by mesenchymal stromal cells (MSC). Exercise potently and transiently mobilizes HSPCs from the bone marrow into peripheral circulation. Thus, the purpose of the present study was to evaluate potential factors in the bone marrow responsible for HSPC mobilization, investigate potential sites of HSPC homing, and asses changes in bone marrow cell populations following exercise. An acute exercise bout increased circulating HSPCs at 15 minutes (88%, P<0.001) that returned to baseline at 60 minutes. Gene expression for HSPC homing factors (CXCL12, vascular endothelial growth factor-a, and angiopoietin-1) were increased at 15 minutes in skeletal muscle and HSPC content was increased in the spleen 48 hours post-exercise (45%, p<0.01). Acute exercise did not alter HSPCs or MSCs quantity in the bone marrow; however, proliferation of HSPCs (40%, p<0.001), multi-potent progenitors (40%, p<0.001), short-term hematopoietic stem cells (61%, p<0.001), long-term hematopoietic stem cells (55%, p=0.002) and MSCs (20%, p=0.01) increased post-exercise. Acute exercise increased the content of the mobilization agent granulocyte-colony stimulating factor, as well as stem cell factor, interleukin-3, and thrombopoeitin in conditioned media collected from bone marrow stromal cells 15 minutes post-exercise. These findings suggest that the MSC secretome is responsible for HSPC mobilization and proliferation; concurrently, HSPCs are homing to extra-medullary sites following exercise.