Combining G-CSF with a blockade of adhesion strongly improves the reconstitutive capacity of mobilized hematopoietic progenitor cells

The monoclonal anti–VLA-4 antibody natalizumab mobilizes CD34+ hematopoietic progenitor cells in humans

“…[13][14][15] Our study demonstrates that the results obtained in these animal models are conferrable with the findings that we made in our patients. In that respect, it is worth noting that the anti-VLA-4-exposed HSCs were capable of reconstituting hematopoiesis in recipient mice following myeloablative conditioning.…”

MT1-MMP and RECK are involved in human CD34+ progenitor cell retention, egress, and mobilization

“…Another potential ligand for CD44 on normal human HPCs is E-selectin (40), shown to regulate cell trafficking and BM lodgment. Earlier studies have demonstrated that administration of anti-CD44 Abs causes mobilization of murine HPCs (41), and combining G-CSF with a blockade of CD44 function improves mobilization efficiencies in mice (42). Based on these data, we suggest that MT1-MMP facilitates progenitor cell release also by antagonizing adhesion interactions, for example CD44-mediated retention.…”

Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC

“…[16,39] In keeping with earlier findings, reduced surface expression of α4 integrin was observed on MPB c-kit+ cells ( [33,35] and data not shown).Reduced α4 expression and α4-mediated adhesion were also reported for CD34+ cells, [40,41] a phenotype which was suggested to favor engraftment, possibly by promoting reversible adhesion and increased migration. [42,43] We additionally tested homing of ssBM and MPB cells treated with or without α4-blocking antibodies. Anti-α4 incubated samples, both ssBM and MPB, showed a similar reduction in marrow homing by 30-40%, so that marrow homing of MPB remained superior to that of ssBM even in the absence of functional α4 integrin (data not shown).…”