Optimized lentiviral transduction of erythroid precursors from healthy adults and patients with myelodysplastic syndromes
Autor: | Thomas Matthes, Lars E. French, Vincent Kindler, Photis Beris, Bernard Chapuis, F Leuba, Vincent Piguet |
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Rok vydání: | 2002 |
Předmět: |
Adult
Cancer Research Genetic enhancement Genetic Vectors Green Fluorescent Proteins CD34 Antigens CD34 Stem cell factor Biology Viral vector Transduction Genetic hemic and lymphatic diseases medicine Humans Erythroid Precursor Cells Myelodysplastic syndromes Genetic Therapy Hematology Hematopoietic Stem Cells medicine.disease Luminescent Proteins medicine.anatomical_structure Oncology Myelodysplastic Syndromes Immunology HIV-1 Cancer research Bone marrow Stem cell |
Zdroj: | Leukemia. 16:1319-1323 |
ISSN: | 1476-5551 0887-6924 |
DOI: | 10.1038/sj.leu.2402527 |
Popis: | Lentivectors, derived from human immunodeficiency virus-1 (HIV-1), represent a novel investigational and therapeutic tool for targeting hematopoietic progenitor cells. We describe a new protocol whereby we achieved a highly efficient lentiviral transduction of erythroid precursor cells originating from the bone marrow of healthy adults and patients with myelodysplastic syndromes (MDS). CD34(+) stem cells from healthy subjects were cultured with erythropoietin, IL-3 and stem cell factor, and thereby expanded approximately 300-fold. When these cultures were transduced with a lentiviral vector expressing GFP as a reporter gene, 70% glycophorin(+) cells were GFP(+). Although proliferation and levels of transduction were reduced in cultures of CD34(+) stem cells from patients with myelodysplastic syndromes, 50% of glycophorin(+) cells became GFP(+), amongst which 30% were sideroblastic erythroid precursors. This study demonstrates that lentiviral vectors are capable of efficiently transducing MDS precursors and offers new perspectives to investigate the influence of specific genes on normal erythroid differentiation. This may eventually help to correct defects in patients suffering from myelodysplastic syndromes. |
Databáze: | OpenAIRE |
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