Abstract
CD34+ stem cells migrate from the bone marrow niche to sites of injury in response to various chemokines. We have investigated the influence of VEGF and complement peptides C3a and C5a, on the stromal derived factor‐1(SDF‐1)‐dependent migration of freshly isolated (from G‐CSF mobilized mononuclear cell preparations) and cord‐blood derived CD34+ stem cells. Freshly isolated CD34+ cells migrated in a dose‐dependent manner in response to SDF‐1, but were unable to migrate to the complement peptides C3a or C5a alone. However, both complement split products augmented the migration of CD34+ cells in response to low concentrations of SDF‐1. This augmented migration behavior was abrogated when CD34+ cells were incubated with anti‐C3a or anti‐C5a antibodies. Flow cytometry demonstrated that CD34+ stem cell express both the C3a and C5a receptors, and anti‐receptor antibodies also mitigated this synergy. Freshly isolated CD34+ cells responded initially to VEGF, but this response diminished after 1–2 days In contrast, with cultured cord blood‐derived CD34+ cells, we observed enhanced migration to SDF‐1 in the presence of VEGF compared to SDF‐1 alone. In conclusion, the migration of CD34+ stem cells depends on their source and ex vivo treatment, and may be enhanced to ischemic tissues (where SDF‐1 is produced) under the influence of other inflammatory and angiogenic signals.
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