Mechanisms of hematopoietic stem cell mobilization: when innate immunity assails the cells that make blood and bone.
Mobilization is now used worldwide to collect large numbers of hematopoietic stem and progenitor cells (HSPCs) for transplantation. Although the first mobilizing agents were discovered largely by accident, discovery of more efficient mobilizing agents will require a better understanding of the molecular mechanisms responsible. During the past 5 years, a number of mechanisms have been identified, shedding new light on the dynamics of the hematopoietic system in vivo and on the intricate relationship between hematopoiesis, innate immunity, and bone. After briefly reviewing the mechanisms by which circulating HSPCs home into the bone marrow and what keeps them there, the current knowledge of mechanisms responsible for HSPC mobilization in response to hematopoietic growth factors such as granulocyte colony-stimulating factor, chemotherapy, chemokines, and polyanions will be discussed together with current strategies developed to further increase HSPC mobilization.
Winkler
Ingrid G
IG
Haematopoietic Stem Cell Laboratory, Cancer Biotherapies Program, Mater Medical Research Institute, University of Queensland, South Brisbane, Queensland, Australia.
Lévesque
Jean-Pierre
JP
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D016723:Bone Remodeling; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007113:Immunity, Innate; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D010012:Osteogenesis; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019010:Vascular Cell Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020780:Matrix Metalloproteinase 9