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Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4
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Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4
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Journal Article
Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4
2012
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Biological and medical sciences
/ Granulocyte colony-stimulating factor
/ Hematologic and hematopoietic diseases
/ Hematopoietic Stem Cell Mobilization
/ Hematopoietic Stem Cell Transplantation
/ Humans
/ Integrin alpha4beta1 - antagonists & inhibitors
/ Leukemia
/ Medicine
/ Oncology
