The chemokine stromal cell-derived factor-1 (SDF-1), and its receptor, CXCR-4, have been implicated in the homing and mobilization of human CD34+ cells. We show here that SDF-1 may also be involved in hematopoiesis, promoting the proliferation of human CD34+ cells purified from normal adult peripheral blood (PB). CXCR-4 was expressed on PB CD34+ cells. The amount of CXCR-4 on PB CD34+ cells was 10 times higher when CD34+ cells were purified following overnight incubation. CXCR-4 overexpression was correlated with a primitive PB CD34+ cell subset defined by a CD34high CD38lowCD71lowc-KitlowThy-1+antigenic profile. The functional significance of CXCR-4 expression was ascertained by assessing the promoting effect of SDF-1 on cell cycle, proliferation, and colony formation. SDF-1 alone increased the percentage of CD34+ cells in the S+G2/M phases and sustained their survival. In synergy with cytokines, SDF-1 increased PB CD34+ and CD34highCD38low cell expansion and colony formation. SDF-1 also stimulated the growth of colonies derived from primitive progenitors released from quiescence by anti–TGF-β treatment. Thus, our results shed new light on the potential role of this chemokine in the stem cell engraftment process, which involves migration, adhesion, and proliferation. Furthermore, both adhesion-induced CXCR-4 overexpression and SDF-1 stimulating activity may be of clinical relevance for improving cell therapy settings in stem cell transplantation.

Level IV. Retrospective study.

When possible, early conversion from external to internal fixation improves bone union and functional recovery after war limb injuries in properly selected patients.

No abstract