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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3928-3937.
Prepublished online as a Blood First Edition Paper on August 15, 2006; DOI 10.1182/blood-2006-02-006353.
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Submitted February 28, 2006
Accepted July 20, 2006
SOCS upregulation mobilizes autologous stem cells through
CXCR4 blockade
Oscar M Pello, Maria del Carmen Moreno-Ortiz, Jose M Rodriguez-Frade, Laura Martinez-Munoz, Daniel Lucas, Lucio Gomez, Pilar Lucas, Enrique Samper, Miguel Aracil, Carlos Martinez-A, Antonio Bernad, and Mario Mellado*
Dept of Immunology and Oncology, Centro Nacional de Biotecnologia/CSIC, Madrid, Spain
Department of Immunology and Oncology, Centro Nacional de Biotecnologia/CSIC, Madrid, Spain
* Corresponding author; email: mmellado{at}cnb.uam.es.
The chemokine CXCL12 influences self-renewal and differentiation of hematopoietic stem cell precursors in
bone marrow by directing them toward specific stroma cell
components. CXCL12 upregulates members of the SOCS family
through JAK/STAT activation, a mechanism that attenuates
chemokine responses. SOCS expression may thus modulate
retention of hematopoietic precursors (Sca 1+c
Kit+Lin-. cells) in bone marrow. We
show that in bovine growth hormone transgenic mice and in
growth hormone-treated mice, SOCS upregulation correlated
with a large number of Sca 1+c Kit+Lin- cells in blood. Retroviral transduction of SOCS blocked in vitro migration of
Sca 1+c-Kit+Lin- cells, as well as their capacity to reconstitute lethally-irradiated mice. Furthermore, in lethally-irradiated mice reconstituted with bone marrow infected by a tetracycline-regulated, SOCS-expressing lentiviral vector, doxycycline treatment promoted rapid, extensive precursor mobilization to the periphery. The results indicate that by blocking CXCR4-mediated
functions, SOCS modulate hematopoietic precursor cell retention in bone marrow, and suggest the therapeutic interest of SOCS manipulation in several pathological situations.
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