Enhancing effects of co-transduction of both human erythropoietin receptor and c-kit cDNAs into hematopoietic stem/progenitor cells from cord blood on proliferation and differentiation of erythroid progenitors

M. S. Dai, M. C. Heinrich, Hal Broxmeyer, L. Lu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Steel factor (SLF) and erythropoietin (Epo) play critical roles in erythropoiesis. To evaluate interactive effects of Epo and SLF receptors (R) in erythropoiesis, CD34+ and CD34+++ cord blood cells were transduced with human EpoR and c-kit cDNAs by retroviral mediated gene transfer. Erythroid (BFU-E) colonies derived from CD34+ or CD34+++ cells transduced with either the EpoR or c-kit gene were significantly increased in the presence of interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), Epo, and different concentrations of SLF compared with that from mock transduced cells. This number was further enhanced by co-transduction of both genes. Enhancement was more apparent in the absence of SLF. Cell numbers in individual erythroid colonies were also significantly increased in ceils transduced with both genes compared with cells transduced with a single gene. Short-term liquid culture showed that ex vivo expansion for five days and numbers of CD34+CD71+ cells in expanded cells from single CD34+++ cells co-transduced with both EpoR and c-kit genes were increased compared with those of EpoR or c-kit-transduced cells. These results demonstrate that co-transduction of both c-kit and EpoR enhances the proliferative capacity of erythroid progenitors under cytokine stimulation above that of single-gene transduced cells.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalCytokines, Cellular and Molecular Therapy
Volume6
Issue number1
StatePublished - 2000

Fingerprint

Erythropoietin Receptors
Hematopoietic Stem Cells
Fetal Blood
Complementary DNA
Stem Cell Factor
Genes
Erythropoietin
Erythropoiesis
Erythroid Precursor Cells
Interleukin-3
Granulocyte-Macrophage Colony-Stimulating Factor
Blood Cells
Cell Count
Cytokines

Keywords

  • c-kit
  • EpoR
  • Gene transfer
  • Hematopoietic stem/progenitor cells

ASJC Scopus subject areas

  • Pharmacology
  • Immunology and Allergy
  • Immunology

Cite this

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title = "Enhancing effects of co-transduction of both human erythropoietin receptor and c-kit cDNAs into hematopoietic stem/progenitor cells from cord blood on proliferation and differentiation of erythroid progenitors",
abstract = "Steel factor (SLF) and erythropoietin (Epo) play critical roles in erythropoiesis. To evaluate interactive effects of Epo and SLF receptors (R) in erythropoiesis, CD34+ and CD34+++ cord blood cells were transduced with human EpoR and c-kit cDNAs by retroviral mediated gene transfer. Erythroid (BFU-E) colonies derived from CD34+ or CD34+++ cells transduced with either the EpoR or c-kit gene were significantly increased in the presence of interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), Epo, and different concentrations of SLF compared with that from mock transduced cells. This number was further enhanced by co-transduction of both genes. Enhancement was more apparent in the absence of SLF. Cell numbers in individual erythroid colonies were also significantly increased in ceils transduced with both genes compared with cells transduced with a single gene. Short-term liquid culture showed that ex vivo expansion for five days and numbers of CD34+CD71+ cells in expanded cells from single CD34+++ cells co-transduced with both EpoR and c-kit genes were increased compared with those of EpoR or c-kit-transduced cells. These results demonstrate that co-transduction of both c-kit and EpoR enhances the proliferative capacity of erythroid progenitors under cytokine stimulation above that of single-gene transduced cells.",
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author = "Dai, {M. S.} and Heinrich, {M. C.} and Hal Broxmeyer and L. Lu",
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T1 - Enhancing effects of co-transduction of both human erythropoietin receptor and c-kit cDNAs into hematopoietic stem/progenitor cells from cord blood on proliferation and differentiation of erythroid progenitors

AU - Dai, M. S.

AU - Heinrich, M. C.

AU - Broxmeyer, Hal

AU - Lu, L.

PY - 2000

Y1 - 2000

N2 - Steel factor (SLF) and erythropoietin (Epo) play critical roles in erythropoiesis. To evaluate interactive effects of Epo and SLF receptors (R) in erythropoiesis, CD34+ and CD34+++ cord blood cells were transduced with human EpoR and c-kit cDNAs by retroviral mediated gene transfer. Erythroid (BFU-E) colonies derived from CD34+ or CD34+++ cells transduced with either the EpoR or c-kit gene were significantly increased in the presence of interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), Epo, and different concentrations of SLF compared with that from mock transduced cells. This number was further enhanced by co-transduction of both genes. Enhancement was more apparent in the absence of SLF. Cell numbers in individual erythroid colonies were also significantly increased in ceils transduced with both genes compared with cells transduced with a single gene. Short-term liquid culture showed that ex vivo expansion for five days and numbers of CD34+CD71+ cells in expanded cells from single CD34+++ cells co-transduced with both EpoR and c-kit genes were increased compared with those of EpoR or c-kit-transduced cells. These results demonstrate that co-transduction of both c-kit and EpoR enhances the proliferative capacity of erythroid progenitors under cytokine stimulation above that of single-gene transduced cells.

AB - Steel factor (SLF) and erythropoietin (Epo) play critical roles in erythropoiesis. To evaluate interactive effects of Epo and SLF receptors (R) in erythropoiesis, CD34+ and CD34+++ cord blood cells were transduced with human EpoR and c-kit cDNAs by retroviral mediated gene transfer. Erythroid (BFU-E) colonies derived from CD34+ or CD34+++ cells transduced with either the EpoR or c-kit gene were significantly increased in the presence of interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), Epo, and different concentrations of SLF compared with that from mock transduced cells. This number was further enhanced by co-transduction of both genes. Enhancement was more apparent in the absence of SLF. Cell numbers in individual erythroid colonies were also significantly increased in ceils transduced with both genes compared with cells transduced with a single gene. Short-term liquid culture showed that ex vivo expansion for five days and numbers of CD34+CD71+ cells in expanded cells from single CD34+++ cells co-transduced with both EpoR and c-kit genes were increased compared with those of EpoR or c-kit-transduced cells. These results demonstrate that co-transduction of both c-kit and EpoR enhances the proliferative capacity of erythroid progenitors under cytokine stimulation above that of single-gene transduced cells.

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