(A) Retention of human CD34+ HSPCs via SDF-1/CXCR4 interactions, CD44/HA interactions, and inhibition of MT1-MMP and MMP2/9 by RECK, all leading to tissue-anchored, quiescent CD34+ HSPCs. (B) G-CSF-induced mobilization of human CD34+ HSPCs via activation of osteoclasts, proteloytic enzymes (including up-regulation of surface MT1-MMP), cleavage of CD44 and SDF-1, and CXCR4 up-regulation, leading to CD34+ HSPC proliferation, differentiation, and increased recruitment to the circulation. (C) Homing of human CD34+ HSPCs in transplanted, immune-deficient NOD/SCID mice preconditioned with total body irradiation. Increased SDF-1 levels in the murine bone marrow endothelium and endosteum region attract human CD34+/CXCR4+ HSPC, while CXCR4-/low HSPCs are mostly trapped in the circulation