Bioactive Sphingolipids and Complement Cascade as New Emerging Regulators of Stem Cell Mobilization and Homing

The α-chemokine stromal derived factor-1 (SDF-1) - seven transmembrane span receptor CXCR4 axis plays a crucial role in retention of hematopoietic stem progenitor cells (HSPCs) in BM. However, the mechanisms that govern mobilization/release of HSPCs from bone marrow (BM) into peripheral blood (PB) and direct a reverse process of their homing back into BM microenvironment after transplantation are still poorly understood. Augmenting evidence demonstrates that during both mobilization and myeloablative conditioning for transplantation a proteolytic microenvironment is induced in BM and complement cascade (CC) becomes activated. In this review we will present augmenting evidence that as result of induction of proteolytis microenvironment as well as CC activation bioactive sphingolipids - sphingosine - 1 phosphate (S1P) and ceramide-1-phosphate (C1P) together with CC cleavage fragments (C3a, C5a and C5b-C9) orchestrate both homing and mobilization of HSCPs.