Back to Search
Start Over
Accelerated lymphocyte reconstitution and long-term recovery after transplantation of lentiviral-transduced rhesus CD34+ cells mobilized by G-CSF and plerixafor.
- Source :
-
Experimental hematology [Exp Hematol] 2011 Jul; Vol. 39 (7), pp. 795-805. Date of Electronic Publication: 2011 Apr 15. - Publication Year :
- 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.<br />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.<br />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 factor-mobilized grafts. Lymphocyte engraftment was accelerated in animals receiving the G-CSF and plerixafor-mobilized 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.<br />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.<br /> (Published by Elsevier Inc.)
- Subjects :
- Animals
Antigens, CD34 metabolism
Benzylamines
Cyclams
Drug Synergism
Flow Cytometry
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Hematopoietic Stem Cells metabolism
Interleukin-3 Receptor alpha Subunit metabolism
Lentivirus genetics
Lymphocytes cytology
Macaca mulatta
Time Factors
Granulocyte Colony-Stimulating Factor pharmacology
Hematopoietic Stem Cell Mobilization methods
Hematopoietic Stem Cell Transplantation methods
Hematopoietic Stem Cells drug effects
Heterocyclic Compounds pharmacology
Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2399
- Volume :
- 39
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Experimental hematology
- Publication Type :
- Academic Journal
- Accession number :
- 21549175
- Full Text :
- https://doi.org/10.1016/j.exphem.2011.04.002