title: Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4.
abstract: Successful hematopoietic stem cell transplant requires the infusion of a sufficient number of hematopoietic stem/progenitor cells (HSPCs) that are capable of homing to the bone marrow cavity and regenerating durable trilineage hematopoiesis in a timely manner. Stem cells harvested from peripheral blood are the most commonly used graft source in HSCT. Although granulocyte colony-stimulating factor (G-CSF) is the most frequently used agent for stem cell mobilization, the use of G-CSF alone results in suboptimal stem cell yields in a significant proportion of patients. Both the chemokine receptor CXCR4 and the integrin α(4)β(1) (very late antigen 4 (VLA-4)) have important roles in the homing and retention of HSPCs within the bone marrow microenvironment. Preclinical and/or clinical studies have shown that targeted disruption of the interaction of CXCR4 or VLA-4 with their ligands results in the rapid and reversible mobilization of hematopoietic stem cells into the peripheral circulation and is synergistic when combined with G-CSF. In this review, we discuss the development of small-molecule CXCR4 and VLA-4 inhibitors and how they may improve the utility and convenience of peripheral blood stem cell transplantation.
authors: Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA.
authors: M P
authors: MP
authors: Rettig
authors: G
authors: G
authors: Ansstas
authors: J F
authors: JF
authors: DiPersio
mesh_terms: D019070:Cell Lineage; D002986:Clinical Trials as Topic; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: C527276:CXCR4 protein, human; D039041:Integrin alpha4beta1; D019718:Receptors, CXCR4