Serial transplantations in nonobese diabetic/severe combined immunodeficiency mice of transduced human CD34+ cord blood cells: Efficient oncoretroviral gene transfer and ex vivo expansion under serum-free conditions

Loretta Gammaitoni, Simona Lucchi, Stefania Bruno, Melania Tesio, Monica Gunetti, Ymera Pignochino, Giorgia Migliardi, Lorenza Lazzari, Massimo Aglietta, Paolo Rebulla, Wanda Piacibello

Research output: Contribution to journalArticle

Abstract

Stable oncoretroviral gene transfer into hematopoietic stem cells (HSCs) provides permanent genetic disease correction. It is crucial to transplant enough transduced HSCs to compete with and replace the defective host hemopoiesis. To increase the number of transduced cells, the role of ex vivo expansion was investigated. For a possible clinical application, all experiments were carried out in serum-free media. A low-affinity nerve growth factor receptor (LNGFR) pseudotyped murine retroviral vector was used to transduce cord blood CD34+ cells, which were then expanded ex vivo. These cells engrafted up to three generations of serially transplanted nonobese diabetic/severe combined immunodeficiency mice: 54.26% ± 5.59%, 19.05% ± 2.01%, and 6.15% ± 5.16% CD45+ cells from primary, secondary, and tertiary recipient bone marrow, respectively, were LNGFR +. Repopulation in secondary and tertiary recipients indicates stability of transgene expression and long-term self-renewal potential of transduced HSCs, suggesting that retroviral gene transfer into HSCs, followed by ex vivo expansion, could facilitate long-term engraftment of genetically modified HSCs.

Original languageEnglish
Pages (from-to)1201-1212
Number of pages12
JournalStem Cells
Volume24
Issue number5
DOIs
Publication statusPublished - May 2006

Keywords

  • Cord blood
  • Expansion Ex vivo gene transfer
  • Gene marking
  • Hematopoietic stem cells
  • Nonobese diabetic/severe combined immunodeficiency mice
  • Oncoretroviral vectors
  • Xenotransplantations

ASJC Scopus subject areas

  • Cell Biology

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