Journal
BONE MARROW TRANSPLANTATION
Volume 45, Issue 10, Pages 1489-1496Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bmt.2009.381
Keywords
hematopoietic stem and progenitor cells; mobilization; natalizumab; G-CSF; migration
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Funding
- Deutsche Forschungsgemeinschaft [SFB655]
- Centre for Regenerative Therapies Dresden
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Therapeutic application of natalizumab, an anti-CD49d Ab, in patients with multiple sclerosis (MS) has been associated with increased levels of circulating CD34+ progenitors. We analyzed the frequency, phenotype and functional activity of CD34+ HSC in blood and BM of patients with MS who were treated with natalizumab. Compared with healthy controls and untreated MS patients, natalizumab treatment increased CD34+ cells in the peripheral blood 7-fold and in BM 10-fold. CD34+ cells derived from blood and marrow of natalizumab-treated patients expressed less of the stem cell marker CD133, were enriched for erythroid progenitors (CFU-E) and expressed lower levels of adhesion molecules than G-CSF-mobilized CD34+ cells. The level of surface CXCR-4 expression on CD34+ cells from patients treated with natalizumab was higher compared with that of CD34+ cells mobilized by G-CSF (median 43.9 vs 15.1%). This was associated with a more than doubled migration capacity toward a chemokine stimulus. Furthermore, CD34+ cells mobilized by natalizumab contained more mRNA for p21 and less for matrix metallopeptidase 9 compared with G-CSF-mobilized hematopoietic stem cell (HSC). Our data indicate that G-CSF and CD49d blockade mobilize different HSC subsets and suggest that both strategies may be differentially applied in specific cell therapy approaches. Bone Marrow Transplantation (2010) 45, 1489-1496; doi:10.1038/bmt.2009.381; published online 25 January 2010
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