Selective enhancement of donor hematopoietic cell engraftment by the CXCR4 antagonist AMD3100 in a mouse transplantation model.
The interaction between stromal cell-derived factor-1 (SDF-1) with CXCR4 chemokine receptors plays an important role in hematopoiesis following hematopoietic stem cell transplantation. We examined the efficacy of post transplant administration of a specific CXCR4 antagonist (AMD3100) in improving animal survival and in enhancing donor hematopoietic cell engraftment using a congeneic mouse transplantation model. AMD3100 was administered subcutaneously at 5 mg/kg body weight 3 times a week beginning at day +2 post-transplant. Post-transplant administration of AMD3100 significantly improves animal survival. AMD3100 reduces pro-inflammatory cytokine/chemokine production. Furthermore, post transplant administration of AMD3100 selectively enhances donor cell engraftment and promotes recovery of all donor cell lineages (myeloid cells, T and B lymphocytes, erythrocytes and platelets). This enhancement results from a combined effect of increased marrow niche availability and greater cell division induced by AMD3100. Our studies shed new lights into the biological roles of SDF-1/CXCR4 interaction in hematopoietic stem cell engraftment following transplantation and in transplant-related mortality. Our results indicate that AMD3100 provides a novel approach for enhancing hematological recovery following transplantation, and will likely benefit patients undergoing transplantation.
Kang
Yubin
Y
Divisions of Hematology, Oncology and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
Chen
Benny J
BJ
Deoliveira
Divino
D
Mito
Jeffrey
J
Chao
Nelson J
NJ
D000818:Animals; D001596:Benzylamines; D000080027:Cyclams; D016207:Cytokines / Q000096:biosynthesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D051379:Mice; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
D001596:Benzylamines; C514936:CXCR4 protein, mouse; D000080027:Cyclams; D016207:Cytokines; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor