Plerixafor+G-CSF-mobilized CD34+ cells represent an optimal graft source for thalassemia gene therapy Journal Article

Authors: Karponi, G.; Psatha, N.; Lederer, C. W.; Adair, J. E.; Zervou, F.; Zogas, N.; Kleanthous, M.; Tsatalas, C.; Anagnostopoulos, A.; Sadelain, M.; Rivière, I.; Stamatoyannopoulos, G.; Yannaki, E.
Article Title: Plerixafor+G-CSF-mobilized CD34+ cells represent an optimal graft source for thalassemia gene therapy
Abstract: Globin gene therapy requires abundant numbers of highly engraftable, autologous hematopoietic stem cells expressing curative levels of β-globin on differentiation. In this study, CD34+ cells from 31 thalassemic patients mobilized with hydroxyurea+granulocyte colony-stimulating factor (G-CSF), G-CSF, Plerixafor, or Plerixafor+G-CSF were transduced with the TNS9.3.55 β-globin lentivector and compared for transducibility and globin expression in vitro, as well as engraftment potential in a xenogeneic model after partial myeloablation. Transduction efficiency and vector copy number (VCN) averaged 48.4 ± 2.8% and 1.91 ± 0.04, respectively, whereas expression approximated the one-copy normal β-globin output. Plerixafor+G-CSF cells produced the highest β-globin expression/VCN. Long-term multilineage engraftment and persistent VCN and vector expression was encountered in all xenografted groups, with Plerixafor+G-CSF-mobilized cells achieving superior short-term engraftment rates, with similar numbers of CD34+ cells transplanted. Overall, Plerixafor+G-CSF not only allows high CD34+ cell yields but also provides increased β-globin expression/VCN and enhanced early human chimerism under nonmyeloablative conditions, thus representing an optimal graft for thalassemia gene therapy. © 2015 by The American Society of Hematology.
Keywords: controlled study; promoter region; nonhuman; t lymphocyte; mouse; gene expression; animal experiment; gene transfer; gene therapy; thalassemia; hemoglobin beta chain; high performance liquid chromatography; granulocyte colony stimulating factor; plerixafor; chromatin assembly and disassembly; expression vector; burst forming unit e; telomere homeostasis; priority journal; article; cd34 + t cell
Journal Title: Blood
Volume: 126
Issue: 5
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2015-07-30
Start Page: 616
End Page: 619
Language: English
DOI: 10.1182/blood-2015-03-629618
PROVIDER: scopus
PMCID: PMC4520876
PUBMED: 26089395
Notes: Export Date: 2 October 2015 -- Source: Scopus
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MSK Authors
  1. Michel W J Sadelain
    449 Sadelain
  2. Isabelle C Riviere
    158 Riviere