Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC
Received 10 July 2006; received in revised form 21 August 2006; accepted 25 September 2006.
Objective
Faster engraftment of G-CSF-mobilized peripheral blood (MPB) transplants compared to steady-state bone marrow (ssBM) is well documented and clinically relevant. A number of different factors likely contribute to this outcome. In the present study we explored whether independent of cell number there are intrinsic differences in the efficiency of progenitor cell homing to marrow between MPB and ssBM.
Methods
Mobilization was achieved by continuous infusion of G-CSF alone or in combination with other mobilizing agents. In vivo homing assays, in vitro migration assays, gene expression analysis, and flow cytometry were utilized to compare homing-related in vivo and in vitro properties of MPB and ssBM HPC.
Results
Marrow homing of murine MPB HPC, generated by different mobilizing schemes, was reproducibly significantly superior to that of ssBM, in lethally irradiated as well as in nonirradiated hosts. This phenotype was independent of MMP9, selectins, and β2- and α4-integrins. Superior homing was also observed for human MPB HPC transplanted into NOD/SCIDβ2microglobulin−/− recipients. Inhibition of HPC migration abrogated the homing advantage of MPB but did not affect homing of ssBM HPC, whereas enhancement of motility by CD26 inhibition improved marrow homing only of ssBM HPC. Enhanced SDF-1-dependent chemotaxis and low CD26 expression on MPB HPC were identified as potential contributing factors. Significant contributions of the putative alternative SDF-1 receptor, RDC1, were unlikely based on gene expression data.
Conclusion
The data suggest increased motility as a converging endpoint of complex changes seen in MPB HPC which is likely responsible for their favorable homing.
Department of Medicine/Hematology, University of Washington, Seattle, Wash., USA
Offprint requests to: Halvard Bonig, M.A., M.D., University of Washington Department of Medicine/Hematology, 1959 NE Pacific Street, Seattle, WA 98195-7720
ABSTRACT