Apr 1, 2003

In vivo expansion of transduced murine hematopoietic cells with a selective amplifier gene

The Journal of Gene Medicine
Akihiro KumeKeiya Ozawa

Abstract

Hematopoietic stem-cell-directed gene transfer has achieved limited success in transducing clinically relevant levels of target cells. The expansion of gene-modified cells is one way to circumvent the problem of inefficient transduction with current vectors. To this end, we have developed 'selective amplifier genes' (SAGs) that encode chimeric proteins that are a fusion of granulocyte colony-stimulating factor receptor and the steroid-binding domain. Prototype SAGs conferred estrogen-responsive growth on murine hematopoietic progenitors. We constructed a retroviral vector coexpressing an SAG for 4-hydroxytamoxifen (Tm)-specific proliferation and the enhanced green fluorescent protein (EGFP). Murine bone marrow cells were transduced with this vector and transplanted into myeloablated mice. Subsequently, recipients were challenged with Tm, and EGFP(+) cells were enumerated. The challenge induced a significant increase in EGFP(+) leukocytes (21 +/- 4% to 27 +/- 5%), while EGFP(+) cells decreased in untreated animals (21 +/- 5% to 10 +/- 3%). Three months later, bone marrow cells were transplanted from the unchallenged mice to secondary hosts. Again the administration of Tm resulted in an increase of EGFP(+) cells (16 +/- 4% to 35 ...Continue Reading

Mentioned in this Paper

Shuttle Vectors
Colony-Forming Units, Hematopoietic
Murine
Granulocyte Count
Granulocyte Colony-Stimulating Factor Receptors
White Blood Cell Count Procedure
Transduction
Transduction, Genetic
Fluorescent stain
Genes, Regulator

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