Increased plasma levels of stromal-derived factor-1 (SDF-1/CXCL12) enhance human thrombopoiesis and mobilize human colony-forming cells (CFC) in NOD/SCID mice

Objective. Stromal-derived factor-1 (SDF-1/CXCL12) is chemotactic for lympho/hematopoietic stem cells. We have previously shown that increasing peripheral blood (PB) levels of SDF-1 with adenovectors expressing human SDF-1 complementary DNA (ad-SDF-1) leads to hematopoietic stem cell mobilization as well as migration of megakaryocytes and thrombocytosis in mice. Herein, we studied the in vivo effects of ad-SDF-1 and of an analogue peptide of SDF-1(CTCE-0214) on human hematopoiesis in a xenotransplant model. Materials and Methods. Sublethally irradiated (300 cGY) NOD/SCID mice transplanted with human cord blood mononuclear cells (CB MNC) were injected with ad-SDF-1 (10(9) plaque forming units, IV, x 1) or CTCE-0214 (10 mg/kg/dose, IV q 24 hours x 7). Effects on megakaryocytopoiesis (CD41(+) cells and platelets) as well as stem cell mobilization were monitored. Results. CB MNC in NOD/SCID mice are able to differentiate into CD41+ cells and platelets, peaking at week 9 at a mean of 3.7 x 10(3)/muL. IV injection of ad-SDF-1 increased human CD41(+) cells by day 4 in PB and was followed by an increase in human platelet production by day 5, with return to baseline by day 30. Human colony-forming cells (CFC) were mobilized from bone marrow to spleen (by day 6-13) and to PB (by day 13). Human CD34(+) and CD33(+), cells were mobilized by this treatment as well. A novel SDF-1 peptide agonist (CTCE-0214) also mobilized human CFC and enhanced human thrombopoiesis. Conclusion. SDF-1 and its analogue may be of clinical value in stimulating platelet recovery after chemo/radiation treatment as well as in stem cell mobilization. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.