Haema 2013; 4(3):201-209
by Pantelis Tsirkinides1, George Boutsikas2, Maria Angelopoulou3
1Attending in Hematology, 401 General Army Hospital of Athens, Department of Hematology,
2Fellow in Hematology, National and Kapodistrian University of Athens, Department of Hematology and Bone Marrow Transplantation,
3Assistant Professor in Hematology, National and Kapodistrian University of Athens, Department of Hematology and Bone Marrow Transplantation, Athens, Greece
Abstract
Following chemotherapy and/or the administration of growth factors, such as G-CSF, the increased circulation of hematopoietic stem cells (HSC) in human blood has been well documented and studied. A number of cells, markers and mechanisms involved in the preservation and mobilization of the HSC have been identified through research over the last four decades. This review aims to systematically present the structure of the HSC “niche” and elucidate the mechanisms of their mobilization, based on current data. However, this field is constantly evolving and new pathways and molecules, such as the sympathetic system, the bone tissue, cannabinoids and sphingolipids have been shown to contribute to the mobilization process of HSC. Understanding the importance and the possible primary pathophysiologic role of each pathway is rather difficult, since they share various overlapping components. In everyday clinical practice, CXCR4 antagonists are now being used as mobilization agents in order to improve HSC mobilization and collection. It appears that the primary initiating event for the mobilization of HSC is chemotherapy-induced endogenous G-CSF production or exogenous G-CSF administration. G-CSF induces proliferation and expansion of the myelomonocytic series, which leads to proteolytic enzyme activation. These enzymes result in disruption of various receptor-ligand bonds, such as the SDF-CXCR4, that leads to the disanchorage of HSC from the bone marrow stroma and their free circulation in blood.