Mobilization of hematopoietic stem cells: state of the art

Abstract

Hematopoietic stem cells (HSCs) normally reside in the bone marrow but can be forced into the blood, a process termed mobilization used clinically to harvest large numbers of HSCs for transplantation. Currently the mobilizing agent of choice is granulocyte colony-stimulating factor; however, not all patients mobilize well. This article reviews recent advances in understanding the molecular mechanisms responsible for the retention of HSCs in the bone marrow, which are perturbed during HSC mobilization, and the clinical application of these findings. The interaction between the chemokine SDF-1/CXCL12 and its receptor CXCR4 is critical to retain HSCs within the bone marrow, leading to the discovery that small synthetic CXCR4 antagonists are potent mobilizing agents that synergize with granulocyte colony-stimulating factor. Separate research has shown that HSC numbers in the bone marrow can be boosted by increasing the number of osteoblasts that support HSCs. HSC mobilization induced by granulocyte colony-stimulating factor may be enhanced by directly targeting the chemotactic interaction between HSCs and bone marrow stroma with CXCR4 antagonists. When the primary problem is reduced, however, HSC numbers in the bone marrow, due to repeated chemotherapy/radiotherapy treatments, an alternative is to enhance HSC content by enhancing bone formation prior to mobilization.