Priming of HSPC as a new strategy to enhance the efficiency of transplantation. (A) SLPs primed homing of murine CFU-GM and CFU-S into bone marrow of lethally irradiated mice. Murine BM-derived Sca-1⁺ cells (10⁵/mouse) were transplanted into lethally irradiated syngeneic mice. Sixteen hours after transplantation, cells were recovered from the femurs and were assayed in secondary cultures for the number of clonogenic CFU-GMs (left panel) and for transplantation into secondarily irradiated animals for the number of day-12 CFU-Ss (right panel). Data are pooled from 3 independent experiments using 10 mice each per tested cells (n = 30) (*P < .0001). No HSPCs were recovered from the marrow cavities of control animals (irradiation; no transplantation). (B) SLPs primed homing of human CB and BM CD34⁺ cells into the bone marrow of lethally irradiated NOD/SCID mice 16 hours after transplantation of human CD34⁺ cells (10⁶)/animal. Mice were killed, and CFU-GM colonies were assayed in methylcellulose cultures. Data are pooled from independent experiments performed on 3 different CB and 3 different BM samples (2-4 mice/tested cell sample) (P < .0001). (C) Schema of SDF-1–CXCR4 axis modulation by various factors. The SDF-1–CXCR4 axis is modulated by various external factors that target, on the one hand, SDF-1 or the N-terminus of CXCR4, which are cleaved by leukocyte-derived proteases, MMPs, or cell surface–expressed CD26/dipeptidylpeptidase IV, and, on the other hand, the SDF-1–CXCR4 axis, which can be primed positively (eg, by PMV, C3a, des-Arg C3a, thrombin, uPAR, fibrinogen, fibronectin, hyaluronic acid, soluble ICAM-1, soluble VCAM-1) or negatively (eg, by polyene antibiotics). Several of these molecules can also be found in tissues affected by inflammation and can modulate the responsiveness of CXCR4⁺ cells to an SDF-1 gradient.