U.S. Department of Defense
Date of this Version
2011
Abstract
Objective. Granulocyte colony-stimulating factor (G-CSF) in combination with plerixafor produces significant mobilization of CD34+ cells in rhesus macaques. We sought to evaluate whether these CD34+ cells can stably reconstitute blood cells with lentiviral gene marking.
Materials and Methods. We performed hematopoietic stem cell transplantation using G-CSF and plerixafor-mobilized rhesus CD34+ cells transduced with a lentiviral vector, and these data were compared with those of G-CSF and stem cell factor mobilization.
Results. G-CSF and plerixafor mobilization resulted in CD34+ cell yields that were twofold higher than yields with G-CSF and stem cell factor. CD123 (interleukin-3 receptor) expression was greater in G-CSF and plerixafor-mobilized CD34+ cells when compared to G-CSF alone. Animals transplanted with G-CSF and plerixafor-mobilized cells showed engraftment of all lineages, similar to animals who received G-CSF and stem cell factorLmobilized grafts. Lymphocyte engraftment was accelerated in animals receiving the G-CSF and plerixaformobilized CD34+ cells. One animal in the G-CSF and plerixafor group developed cold agglutinin-associated skin rash during the first 3 months of rapid lymphocyte recovery. One year after transplantation, all animals had 2% to 10% transgene expression in all blood cell lineages.
Conclusions. G-CSF and plerixafor-mobilized CD34+ cells accelerate lymphocyte engraftment and contain hematopoietic stem cell capable of reconstituting multilineage blood cells. These findings indicate important differences to consider in plerixafor-based hematopoietic stem cell mobilization protocols in rhesus macaques.
Comments
Published in Experimental Hematology (2011) 39:795–805; doi: 10.1016/j.exphem.2011.04.002