| First Author | Pello OM | Year | 2006 |
| Journal | Blood | Volume | 108 |
| Issue | 12 | Pages | 3928-37 |
| PubMed ID | 16912231 | Mgi Jnum | J:140545 |
| Mgi Id | MGI:3814046 | Doi | 10.1182/blood-2006-02-006353 |
| Citation | Pello OM, et al. (2006) SOCS up-regulation mobilizes autologous stem cells through CXCR4 blockade. Blood 108(12):3928-37 |
| abstractText | The chemokine CXCL12 influences self-renewal and differentiation of hematopoietic stem cell precursors in bone marrow by directing them toward specific stromalcell components. CXCL12 up-regulates 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 up-regulation correlated with a large number of Sca-1(+) c-Kit(+)Lin(-) cells in blood. Retroviral transduction of SOCSs 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, SOCSs modulate hematopoietic precursor cell retention in bone marrow, and suggest the therapeutic interest of SOCS manipulation in several pathologic situations. |
