title: Acute exercise mobilizes hematopoietic stem and progenitor cells and alters the mesenchymal stromal cell secretome.
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 assess changes in bone marrow cell populations following exercise. An acute exercise bout increased circulating HSPCs at 15 min (88%, P < 0.001) that returned to baseline at 60 min. Gene expression for HSPC homing factors (CXCL12, vascular endothelial growth factor-a, and angiopoietin-1) were increased at 15 min in skeletal muscle and HSPC content was increased in the spleen 48 h postexercise (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), multipotent 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 postexercise. 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 min postexercise. These findings suggest that the MSC secretome is responsible for HSPC mobilization and proliferation; concurrently, HSPCs are homing to extramedullary sites following exercise.
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Russell
authors.initials: R
authors.lastname: Emmons
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Grace M
authors.initials: GM
authors.lastname: Niemiro
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois.
authors.forename: Olatomide
authors.initials: O
authors.lastname: Owolabi
authors.affiliation: Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, Illinois mdelisio@illinois.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: De Lisio
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D054377:Chemokine CXCL12 / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000502:physiology*; D007377:Interleukin-3 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013926:Thrombopoietin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D054377:Chemokine CXCL12; D007377:Interleukin-3; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin
keywords: hematopoietic stem cell; mesenchymal stromal cells; paracrine factors; secretome