Granulocyte colony stimulating factor expands hematopoietic stem cells within the central but not endosteal bone marrow region

Grassinger, Jochen and Williams, Brenda and Olsen, Gemma H. and Haylock, David N. and Nilsson, Susan K. (2012) Granulocyte colony stimulating factor expands hematopoietic stem cells within the central but not endosteal bone marrow region. CYTOKINE, 58 (2). pp. 218-225. ISSN 1043-4666,

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Abstract

Granulocyte colony stimulating factor (G-CSF) is clinically well established for the mobilization of hematopoietic stem cells (HSC). Extensive data on the underlying mechanism of G-CSF induced mobilization is available; however, little is known regarding the functional effect of G-CSF on HSC within the bone marrow (BM). In this study we analyzed the proportion and number of murine HSC in the endosteal and central bone marrow regions after 4 days of G-CSF administration. We demonstrate that the number of HSC, defined as CD150(+)CD48(-)LSK cells (LSKSLAM cells), increased within the central BM region in response to G-CSF, but not within the endosteal BM region. In addition the level of CD150 and CD48 expression also increased on cells isolated from both regions. We further showed that G-CSF mobilized proportionally fewer LSKSLAM compared to LSK cells, mobilized LSKSLAM had colony forming potential and the presence of these cells can be used as a measure for mobilization efficiency. Together we provide evidence that HSC in the BM respond differently to G-CSF and this is dependent on their location. These findings will be valuable in developing new agents which specifically mobilize HSC from the endosteal BM region, which we have previously demonstrated to have significantly greater hematopoietic potential compared to their phenotypically identical counterparts located in other regions of the BM. (C) 2012 Elsevier Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: BLOOD PROGENITOR CELLS; HIGH-DOSE CHEMOTHERAPY; SLAM FAMILY RECEPTORS; NON-HODGKINS-LYMPHOMA; FACTOR G-CSF; PERIPHERAL-BLOOD; STEM/PROGENITOR CELLS; MULTIPLE-MYELOMA; CXCR4 ANTAGONIST; TERM ENGRAFTMENT; Granulocyte colony stimulating factor; Mobilization; Hematopoietic stem cells
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 18 May 2020 05:16
Last Modified: 18 May 2020 05:16
URI: https://pred.uni-regensburg.de/id/eprint/18832

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