Stromal Cell Derived Factor-1 / CXCL12, CXCR4 and CD26 in the Mobilization and Homing of Hematopoietic Stem and Progenitor Cells
H. E. Broxmeyer,
K. W. Christopherson II.
Hematopoietic Stem (HSC) and Progenitor (HPC) cells are rare and give rise to all blood forming cells. In many malignant and non-malignant disorders, a transplant of HSC / HPC is the only curative regiment available for these disorders. Transplants of HSC / HPC are done through intravenous injection of donor cells into conditioned recipients where the cells home to and engraft in the bone marrow. The majority of HSC / HPC transplants are currently performed with these cells after they are mobilized from the marrow to circulating blood where they are then collected for transplantation. Chemokines are recognized for their chemoattractant / chemotactic capabilities of many different cell types. Stromal Cell Derived Factor-1 (SDF-1 / CXCL12) and its receptor, CXCR4 have been implicated by us and others in the migration in vitro and in vivo of HSC / HPC. This paper reviews the role and practical implications of the SDF- 1 / CXCL12-CXCR4 axis in the homing, engraftment and mobilization of HSC, and the modulation of these events by the cell surface component CD26, which manifests Dipeptidylpeptidase IV (DPPIV) activity that truncates SDF-1 / CXCL12 and changes its activity, and by AMD3100, a specific antagonist of SDF-1 / CXCL12 binding to CXCR4. Inhibition or deletion of CD26 has been used to enhance the homing and engrafting capabilities of murine HSC, while AMD3100 has been used to induce mobilization of murine and human HSC and HPC, and to enhance this mobilization induced by Granulocyte-Colony Stimulating Factor. Further efforts in understanding the SDF-1 / CXCL12-CXCR4 axis, and CD26 and their mechanisms of actions and modulation should yield information of clinical relevance and utility.
Keywords: stem cells, chemokines, cxcl12, cxcr4, cd26, homing, mobilization, chemotaxis, transplantation, cytokines
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