Accelerated lymphocyte reconstitution and long-term recovery after transplantation of lentiviral-transduced rhesus CD34⁺ cells mobilized by G-CSF and plerixafor

Authors

• Naoya Uchida, National Institutes of Health
• Aylin Bonifacino, National Institutes of Health
• Allen E. Krouse, National Institutes of Health
• Mark E. Metzger, National Institutes of Health
• Gyorgy Csako, National Institutes of Health
• Agnes Lee-Stroka, National Institutes of Health
• Ross M. Fasano, National Institutes of Health
• Susan F. Leitman, National Institutes of Health
• Joseph J. Mattapallil, Uniformed Services University of Health Sciences
• Matthew M. Hsieh, National Institutes of Health
• John F. Tisdale, National Institutes of Health
• Robert E. Donahue, National Institutes of HealthFollow

Date of this Version

2011

Comments

Published in Experimental Hematology (2011) 39:795–805; doi: 10.1016/j.exphem.2011.04.002

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.