Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist
| Autor: | P. Artur Plett, Scott Cooper, D. Wade Clapp, Gary Calandra, Xiaxin Li, Hal E. Broxmeyer, David C. Dale, Gary Bridger, Edward F. Srour, Giao Hangoc, Christie M. Orschell, Timothy B. Campbell, W. Conrad Liles, Barbara Graham-Evans |
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| Rok vydání: | 2005 |
| Předmět: |
Benzylamines
Receptors CXCR4 Immunology CD34 Antigens CD34 Mice Inbred Strains Mice SCID Biology Cyclams Article Colony-Forming Units Assay 03 medical and health sciences Mice 0302 clinical medicine Heterocyclic Compounds Granulocyte Colony-Stimulating Factor medicine Immunology and Allergy Animals Humans Progenitor cell Hematopoietic Stem Cell Mobilization 030304 developmental biology 0303 health sciences Plerixafor Hematopoietic stem cell Drug Synergism Hematopoietic Stem Cells Chemokine CXCL12 Haematopoiesis medicine.anatomical_structure embryonic structures Cancer research Bone marrow Stem cell Chemokines CXC 030215 immunology medicine.drug |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Popis: | Improving approaches for hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) mobilization is clinically important because increased numbers of these cells are needed for enhanced transplantation. Chemokine stromal cell derived factor-1 (also known as CXCL12) is believed to be involved in retention of HSCs and HPCs in bone marrow. AMD3100, a selective antagonist of CXCL12 that binds to its receptor, CXCR4, was evaluated in murine and human systems for mobilizing capacity, alone and in combination with granulocyte colony-stimulating factor (G-CSF). AMD3100 induced rapid mobilization of mouse and human HPCs and synergistically augmented G-CSF–induced mobilization of HPCs. AMD3100 also mobilized murine long-term repopulating (LTR) cells that engrafted primary and secondary lethally-irradiated mice, and human CD34+ cells that can repopulate nonobese diabetic-severe combined immunodeficiency (SCID) mice. AMD3100 synergized with G-CSF to mobilize murine LTR cells and human SCID repopulating cells (SRCs). Human CD34+ cells isolated after treatment with G-CSF plus AMD3100 expressed a phenotype that was characteristic of highly engrafting mouse HSCs. Synergy of AMD3100 and G-CSF in mobilization was due to enhanced numbers and perhaps other characteristics of the mobilized cells. These results support the hypothesis that the CXCL12-CXCR4 axis is involved in marrow retention of HSCs and HPCs, and demonstrate the clinical potential of AMD3100 for HSC mobilization. |
| Databáze: | OpenAIRE |
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