BIO5192, a small molecule inhibitor of VLA-4, mobilizes hematopoietic stem and progenitor cells

Pablo Ramirez, Michael P. Rettig, Geoffrey L. Uy, Elena Deych, Matthew S. Holt, Julie K. Ritchey, John F. DiPersio

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

Abstract

Here we show that interruption of the VCAM-1/VLA-4 axis with a small molecule inhibitor of VLA-4, BIO5192, results in a 30-fold increase in mobilization of murine hematopoietic stem and progenitors (HSPCs) over basal levels. An additive affect on HSPC mobilization (3-fold) was observed when plerixa for (AMD3100), a small molecule inhibitor of the CXCR-4/SDF-1 axis, was combined with BIO5192. Furthermore, the combination of granulocyte colony-stimulating factor (G-CSF), BIO5192, and plerixafor enhanced mobilization by 17-fold compared with G-CSF alone. HSPCs mobilized by BIO5192 or the combination of BIO5192 and plerixafor mobilized long-term repopulating cells, which successfully engraft and expand in a multilineage fashion in secondary transplantation recipients. Splenectomy resulted in a dramatic enhancement of G-CSF-induced mobilization while decreasing both plerixafor- and BIO5192-induced mobilization of HSPCs. These data provide evidence for the utility of small molecule inhibitors of VLA-4 either alone or in combination with G-CSF or AMD3100 for mobilization of hematopoietic stem and progenitor cells.

Original languageEnglish
Pages (from-to)1340-1343
Number of pages4
JournalBlood
Volume114
Issue number7
DOIs
StatePublished - 2009

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