AMD3100 mobilizes endothelial progenitor cells in mice, but inhibits its biological functions by blocking an autocrine/paracrine regulatory loop of stromal cell derived factor-1 in vitro.

Endothelial progenitor cells (EPCs), a CXCR4-bearing cell line, are thought to positively influence reendothelialization, vascular repair, and angiogenesis. AMD3100, a highly selective antagonist of stromal cell derived factor (SDF)-1 that binds to its receptor, CXCR4, has been shown to induce rapid mobilization of hematopoietic stem cells in mice, dogs, and humans. Results of this study indicate that AMD3100 injection can induce a rapid and potent mobilization of EPCs in mice compared with saline injection. The study demonstrates that murine spleen-derived EPCs can produce high levels of SDF-1 in vitro. Blocking this endogenous SDF-1 with AMD3100 decreases the number of EPCs; inhibits the proliferation, migration, and adhesion of EPCs; and induces EPC apoptosis. In addition, AMD3100 inhibits ectogenous SDF-1alpha induced improvement of EPC functions. However, AMD3100 incubation does not change the functions of CXCR4-negative cell line HPDE6. In conclusion, AMD3100 can be regarded as a potent mobilizer of EPCs in mice. EPCs have an autocrine/paracrine SDF-1 loop, and breaking this loop with AMD3100 can inhibit the EPC functions in vitro.