The a-chemokine stromal derived factor 1 (SDF-1), which binds to the CXCR4 and CXCR7 receptors, directs migration and\r\nhoming of CXCR4 hematopoietic stem/progenitor cells (HSPCs) to bone marrow (BM) and plays a crucial role in retention of\r\nthese cells in stem cell niches. However, this unique role of SDF-1 has been recently challenged by several observations supporting\r\nSDF-1-CXCR4-independent BM homing. Specifically, it has been demonstrated that HSPCs respond robustly to some bioactive\r\nlipids, such as sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), and migrate in response to gradients of certain\r\nextracellular nucleotides, including uridine triphosphate (UTP) and adenosine triphosphate (ATP). Moreover, the responsiveness\r\nof HSPCs to an SDF-1 gradient is enhanced by some elements of innate immunity (e.g., C3 complement cascade cleavage fragments\r\nand antimicrobial cationic peptides, such as cathelicidin/LL-37 or �Ÿ2-defensin) as well as prostaglandin E2 (PGE2). Since all these\r\nfactors are upregulated in BM aftermyeloblative conditioning for transplantation, a more complex picture of homing emerges that\r\ninvolves several factors supporting, and in some situations even replacing, the SDF-1-CXCR4 axis.
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