[Study on expression and resistance of the double drug resistance genes transduced into human umbilical cord blood CD34+ cells mediated by bicistronic retroviral vector]

Shi Yan Sheng Wu Xue Bao. 2000 Dec;33(4):341-8.
[Article in Chinese]

Abstract

To explore whether human umbilical cord blood CD34+ cells transduced with human aldehyde dehydrogenase class-1 (ALDH1) and multidrug resistance gene (MDR1) increase resistance to 4-Hyaroxycyclophosphophamide (4-HC) and P-Glycoprotein Effluxed Drugs, a bicistronic Retroviral vector G1Na-ALDH1-IRES-MDR1 was constructed. The vector was transduced into the packaging cell lines GP + E86 and PA317 by LipofectAMINE. Using the medium containing VCR and 4-HC for cloning selection and pingponging supernatant infection between ecotropic producer clone and amphotropic producer clone, we obtained high titer amphotropic PA317 producer clone with the highest titer up to 5.6 x 10(5) CFU/ml. Cord blood CD34+ cells were transfectced repeatedly with supernatant of retrovirus containing human ALDH1 and MDR1cDNA under stimulation of hemopoietie growth factors. PCR, RT-PCR, Southern blot, Northern blot, FACS and MTT method analyses show that dual drug resistance genes have been integrated into the genomic DNA of cord blood CD34+ cells and expressed efficiently. The transgenes recipient cells confered 4- to 7.2-folds stronger resistance to cyclophospsphamede and P-Glycoprotein Effluxes drug in comparison with the nontransduced cells. This study provided a foundation for the application of combination chemotherapy in tumor clinical trial.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Aldehyde Dehydrogenase / genetics*
  • Aldehyde Dehydrogenase 1 Family
  • Antigens, CD34 / analysis*
  • Cells, Cultured
  • Fetal Blood / cytology*
  • Gene Expression
  • Gene Transfer Techniques
  • Genes, MDR*
  • Genetic Therapy
  • Genetic Vectors
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Isoenzymes / genetics*
  • Retinal Dehydrogenase
  • Retroviridae / genetics*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antigens, CD34
  • Isoenzymes
  • Aldehyde Dehydrogenase 1 Family
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase