The role of complement in the trafficking of hematopoietic stem/progenitor cells

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Transplantation of hematopoietic stem/progenitor cells (HSPC) has become a well-established treatment for various malignant and non-malignant hematological disorders and certain solid tumors. Approximately 60,000 autologous and allogeneic HSPC transplants are performed annually worldwide. Characteristics of HSPC that make clinical transplantation feasible, apart from their regenerative potential, include their ability to be coaxed out of the bone marrow (BM), or “mobilize”, and their capacity to “home” back to the marrow space after intravenous infusion. In our investigations of HSPC mobilization and homing, the complement system has emerged as an important, yet underappreciated, modulator of this bidirectional trafficking of HSPC. Although many factors contribute to HSPC mobilization and homing, here, we focus on the role of complement cascade (CC) components C1q, C3a, C5a and C5b-C9 (membrane attack complex; MAC) and infer that their modulation in the future could have significance to improve outcomes of HSPC transplantation. After autologous and allogeneic transplantation the patient requirements for red blood cell transfusion are high (median 12; range: 8–16 units per patient),1 and despite variations in practice, there is also substantial need for platelet transfusions (median 5; range 0–110 units per patient).2 Hence, improving the strategies for HSPC collection based on better understanding of the mechanisms of mobilization and homing could also reduce the utilization of blood products.