Influence of interleukin-3, interleukin-6, and stem cell factor on retroviral transduction of rhesus monkey CD34+ hematopoietic progenitor cells measured in vitro and in vivo

V W van Beusechem, J A Bart-Baumeister, P M Hoogerbrugge, D Valerio

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

As a preclinical test for bone marrow gene therapy, we transduced Rhesus monkey CD34+CD11b- hematopoietic progenitor cells with recombinant retroviruses. We investigated the effects of the recombinant hematopoietic growth factors interleukin-3 (IL-3), interleukin-6 (IL-6) and stem cell factor (SCF) on the susceptibility of in vitro clonogenic progenitor cells and in vivo repopulating stem cells to retroviral transduction. IL-6 did not contribute to transduction of progenitor cells, whereas IL-3 and SCF supported expansion and transduction of progenitors. The combination of IL-3 and IL-6 was most efficient at promoting transduction of more mature progenitor cell types. Cultures containing IL-6+SCF yielded optimal maintenance of CD34+CD11b- cells without evidence for lineage-restricted maturation. Autologous transplantation of transduced grafts cultured in the presence of SCF, with or without IL-3 or IL-6, into lethally irradiated Rhesus monkeys resulted in a severely delayed hematopoietic reconstitution as compared with grafts transduced in the presence of IL-3 alone. After in vivo repopulation, transduced cells were found among peripheral blood mononuclear cells, granulocytes and CD34+CD11b- progenitor cells in the bone marrow of engrafted animals. However, no significant difference in transduction efficiency on in vivo repopulating stem cells could be demonstrated among the tested growth factor conditions.

Original languageEnglish
Pages (from-to)245-55
Number of pages11
JournalGene Therapy
Volume2
Issue number4
Publication statusPublished - Jun 1995

Cite this

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title = "Influence of interleukin-3, interleukin-6, and stem cell factor on retroviral transduction of rhesus monkey CD34+ hematopoietic progenitor cells measured in vitro and in vivo",
abstract = "As a preclinical test for bone marrow gene therapy, we transduced Rhesus monkey CD34+CD11b- hematopoietic progenitor cells with recombinant retroviruses. We investigated the effects of the recombinant hematopoietic growth factors interleukin-3 (IL-3), interleukin-6 (IL-6) and stem cell factor (SCF) on the susceptibility of in vitro clonogenic progenitor cells and in vivo repopulating stem cells to retroviral transduction. IL-6 did not contribute to transduction of progenitor cells, whereas IL-3 and SCF supported expansion and transduction of progenitors. The combination of IL-3 and IL-6 was most efficient at promoting transduction of more mature progenitor cell types. Cultures containing IL-6+SCF yielded optimal maintenance of CD34+CD11b- cells without evidence for lineage-restricted maturation. Autologous transplantation of transduced grafts cultured in the presence of SCF, with or without IL-3 or IL-6, into lethally irradiated Rhesus monkeys resulted in a severely delayed hematopoietic reconstitution as compared with grafts transduced in the presence of IL-3 alone. After in vivo repopulation, transduced cells were found among peripheral blood mononuclear cells, granulocytes and CD34+CD11b- progenitor cells in the bone marrow of engrafted animals. However, no significant difference in transduction efficiency on in vivo repopulating stem cells could be demonstrated among the tested growth factor conditions.",
keywords = "Animals, Antigens, CD34/genetics, Bone Marrow/physiology, Cells, Cultured, DNA, Viral/genetics, Hematopoietic Cell Growth Factors/pharmacology, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells/physiology, Humans, Interleukin-3/pharmacology, Interleukin-6/pharmacology, Macaca mulatta, Recombinant Proteins/pharmacology, Retroviridae/genetics, Stem Cell Factor/pharmacology, Transduction, Genetic, Transplantation, Autologous",
author = "{van Beusechem}, {V W} and Bart-Baumeister, {J A} and Hoogerbrugge, {P M} and D Valerio",
year = "1995",
month = "6",
language = "English",
volume = "2",
pages = "245--55",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "4",

}

Influence of interleukin-3, interleukin-6, and stem cell factor on retroviral transduction of rhesus monkey CD34+ hematopoietic progenitor cells measured in vitro and in vivo. / van Beusechem, V W; Bart-Baumeister, J A; Hoogerbrugge, P M; Valerio, D.

In: Gene Therapy, Vol. 2, No. 4, 06.1995, p. 245-55.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Influence of interleukin-3, interleukin-6, and stem cell factor on retroviral transduction of rhesus monkey CD34+ hematopoietic progenitor cells measured in vitro and in vivo

AU - van Beusechem, V W

AU - Bart-Baumeister, J A

AU - Hoogerbrugge, P M

AU - Valerio, D

PY - 1995/6

Y1 - 1995/6

N2 - As a preclinical test for bone marrow gene therapy, we transduced Rhesus monkey CD34+CD11b- hematopoietic progenitor cells with recombinant retroviruses. We investigated the effects of the recombinant hematopoietic growth factors interleukin-3 (IL-3), interleukin-6 (IL-6) and stem cell factor (SCF) on the susceptibility of in vitro clonogenic progenitor cells and in vivo repopulating stem cells to retroviral transduction. IL-6 did not contribute to transduction of progenitor cells, whereas IL-3 and SCF supported expansion and transduction of progenitors. The combination of IL-3 and IL-6 was most efficient at promoting transduction of more mature progenitor cell types. Cultures containing IL-6+SCF yielded optimal maintenance of CD34+CD11b- cells without evidence for lineage-restricted maturation. Autologous transplantation of transduced grafts cultured in the presence of SCF, with or without IL-3 or IL-6, into lethally irradiated Rhesus monkeys resulted in a severely delayed hematopoietic reconstitution as compared with grafts transduced in the presence of IL-3 alone. After in vivo repopulation, transduced cells were found among peripheral blood mononuclear cells, granulocytes and CD34+CD11b- progenitor cells in the bone marrow of engrafted animals. However, no significant difference in transduction efficiency on in vivo repopulating stem cells could be demonstrated among the tested growth factor conditions.

AB - As a preclinical test for bone marrow gene therapy, we transduced Rhesus monkey CD34+CD11b- hematopoietic progenitor cells with recombinant retroviruses. We investigated the effects of the recombinant hematopoietic growth factors interleukin-3 (IL-3), interleukin-6 (IL-6) and stem cell factor (SCF) on the susceptibility of in vitro clonogenic progenitor cells and in vivo repopulating stem cells to retroviral transduction. IL-6 did not contribute to transduction of progenitor cells, whereas IL-3 and SCF supported expansion and transduction of progenitors. The combination of IL-3 and IL-6 was most efficient at promoting transduction of more mature progenitor cell types. Cultures containing IL-6+SCF yielded optimal maintenance of CD34+CD11b- cells without evidence for lineage-restricted maturation. Autologous transplantation of transduced grafts cultured in the presence of SCF, with or without IL-3 or IL-6, into lethally irradiated Rhesus monkeys resulted in a severely delayed hematopoietic reconstitution as compared with grafts transduced in the presence of IL-3 alone. After in vivo repopulation, transduced cells were found among peripheral blood mononuclear cells, granulocytes and CD34+CD11b- progenitor cells in the bone marrow of engrafted animals. However, no significant difference in transduction efficiency on in vivo repopulating stem cells could be demonstrated among the tested growth factor conditions.

KW - Animals

KW - Antigens, CD34/genetics

KW - Bone Marrow/physiology

KW - Cells, Cultured

KW - DNA, Viral/genetics

KW - Hematopoietic Cell Growth Factors/pharmacology

KW - Hematopoietic Stem Cell Transplantation

KW - Hematopoietic Stem Cells/physiology

KW - Humans

KW - Interleukin-3/pharmacology

KW - Interleukin-6/pharmacology

KW - Macaca mulatta

KW - Recombinant Proteins/pharmacology

KW - Retroviridae/genetics

KW - Stem Cell Factor/pharmacology

KW - Transduction, Genetic

KW - Transplantation, Autologous

M3 - Article

VL - 2

SP - 245

EP - 255

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 4

ER -