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 Blood, 1 October 2006, Vol. 108, No. 7, pp. 2190-2197.
Prepublished online as a Blood First Edition Paper on June 1, 2006; DOI 10.1182/blood-2005-12-010272.

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HEMATOPOIESIS

Increased hematopoietic stem cell mobilization in aged mice

Zhenlan Xing, Marnie A. Ryan, Deidre Daria, Kalpana J. Nattamai, Gary Van Zant, Lei Wang, Yi Zheng, and Hartmut Geiger

From the Division of Experimental Hematology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH; and the Departments of Internal Medicine and Physiology, Markey Cancer Center, University of Kentucky, Lexington, KY.

Hematopoietic stem and progenitor cells (HSPCs) are located in the bone marrow in close association with a highly organized 3-dimensional structure formed by stroma cells, referred to as the niche. Mobilization of HSPCs from bone marrow to peripheral blood in response to granulocyte colony-stimulating factor (G-CSF) requires de-adhesion of HSPCs from the niche. The influence of aging of HSPCs on cell-stroma interactions has not been determined in detail. Using a mouse model of G-CSF–induced mobilization, we demonstrated that the ability to mobilize hematopoietic stem cells is approximately 5-fold greater in aged mice. Competitive mobilization experiments confirmed that enhanced mobilization ability was intrinsic to the stem cell. Enhanced mobilization efficiency of primitive hematopoietic cells from aged mice correlated with reduced adhesion of hematopoietic progenitor cells to stroma and with elevated levels of GTP-bound Cdc42. These results might indicate that stroma–stem cell interactions are dynamic over a lifetime and result in physiologically relevant changes in the biology of primitive hematopoietic cells with age.


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