Accelerated lymphocyte reconstitution and long-term recovery after transplantation of lentiviral-transduced rhesus CD34\u3csup\u3e+\u3c/sup\u3e cells mobilized by G-CSF and plerixafor

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