Human peripheral blood hematopoietic progenitors are optimal targets of retroviral-mediated gene transfer

Marco Bregni, Michele Magni, Salvatore Siena, Massimo Di Nicola, Gianni Bonadonna, Alessandro Massimo Gianni

Research output: Contribution to journalArticlepeer-review

Abstract

Hematopoietic progenitor cells circulate in the peripheral blood (PB) of cancer patients during the recovery phase that follows treatment with high-dose cyclophosphamide followed by hematopoietic growth factor infusion. We report that when PB progenitors were exposed in vitro to filtered supernatant from cell line PA317-N2, producing amphotropic helper-free N2 vector at conventional titers, successful retroviral-mediated transfer of neomycin resistance gene was documented by polymerase chain reaction in 93% of day 14 myelomonocytic colonies. Under the same conditions, gene transfer was achieved in 22% of steady-state bone marrow-derived myelomonocytic colonies. Neo-resistance gene transfer was documented also in a CD34+/cyclophosphamide-resistant precursor to granulocyte-macrophage colonies, an undifferentiated progenitor close to the hematopoietic stem cell. Neither cocultivation with vector-producing cells nor high vector titer were stringent requisites for efficient gene transfer. The large-scale availability of PB hematopoietic progenitors in cancer patients, together with the high gene transfer rate achieved under safe and clinically feasible conditions, support an optimal approach for gene transfer procedures into the human hematopoietic system.

Original languageEnglish
Pages (from-to)1418-1422
Number of pages5
JournalBlood
Volume80
Issue number6
Publication statusPublished - Sep 15 1992

ASJC Scopus subject areas

  • Hematology

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