Identification of human and mouse hematopoietic stem cell populations expressing high levels of mRNA encoding retrovirus receptors

Donald Orlic, Laurie J. Girard, Stacie M. Anderson, Louise C. Pyle, Mervin Yoder, Hal Broxmeyer, David M. Bodine

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

One obstacle to retrovirus-mediated gene therapy for human hematopoietic disorders is the low efficiency of gene transfer into pluripotent hematopoietic stem cells (HSC). We have previously shown a direct correlation between retrovirus receptor mRNA levels in mouse HSC and the efficiency with which they are transduced. In the present study, we assayed retrovirus receptor mRNA levels in a variety of mouse and human HSC populations to identify HSC which may be more competent for retrovirus transduction. The highest levels of amphotropic retrovirus receptor (amphoR) mRNA were found in cryopreserved human cord blood HSC. The level of amphoR mRNA in Lin- CD34+ CD38- cells isolated from frozen cord blood was 12-fold higher than the level in fresh cord blood Lin- CD34+ CD38- cells. In mice, the level of amphoR mRNA in HSC from the bone marrow (BM) of mice treated with stem cell factor and granulocyte-colony stimulating factor was 2.8- to 7.8-fold higher than in HSC from the BM of untreated mice. These findings suggest that HSC from frozen cord blood and cytokine-mobilized BM may be superior targets for amphotropic retrovirus transduction compared with HSC from untreated adult BM.

Original languageEnglish (US)
Pages (from-to)3247-3254
Number of pages8
JournalBlood
Volume91
Issue number9
StatePublished - May 1 1998
Externally publishedYes

Fingerprint

Forensic Anthropology
Retroviridae
Hematopoietic Stem Cells
Stem cells
Messenger RNA
Population
Fetal Blood
Bone
Blood
Bone Marrow
Gene transfer
Gene therapy
Pluripotent Stem Cells
Stem Cell Factor
Granulocyte Colony-Stimulating Factor
Genetic Therapy
Cytokines

ASJC Scopus subject areas

  • Hematology

Cite this

Identification of human and mouse hematopoietic stem cell populations expressing high levels of mRNA encoding retrovirus receptors. / Orlic, Donald; Girard, Laurie J.; Anderson, Stacie M.; Pyle, Louise C.; Yoder, Mervin; Broxmeyer, Hal; Bodine, David M.

In: Blood, Vol. 91, No. 9, 01.05.1998, p. 3247-3254.

Research output: Contribution to journalArticle

Orlic, Donald ; Girard, Laurie J. ; Anderson, Stacie M. ; Pyle, Louise C. ; Yoder, Mervin ; Broxmeyer, Hal ; Bodine, David M. / Identification of human and mouse hematopoietic stem cell populations expressing high levels of mRNA encoding retrovirus receptors. In: Blood. 1998 ; Vol. 91, No. 9. pp. 3247-3254.
@article{393a8ec9e06d4aa28a31182b625028a6,
title = "Identification of human and mouse hematopoietic stem cell populations expressing high levels of mRNA encoding retrovirus receptors",
abstract = "One obstacle to retrovirus-mediated gene therapy for human hematopoietic disorders is the low efficiency of gene transfer into pluripotent hematopoietic stem cells (HSC). We have previously shown a direct correlation between retrovirus receptor mRNA levels in mouse HSC and the efficiency with which they are transduced. In the present study, we assayed retrovirus receptor mRNA levels in a variety of mouse and human HSC populations to identify HSC which may be more competent for retrovirus transduction. The highest levels of amphotropic retrovirus receptor (amphoR) mRNA were found in cryopreserved human cord blood HSC. The level of amphoR mRNA in Lin- CD34+ CD38- cells isolated from frozen cord blood was 12-fold higher than the level in fresh cord blood Lin- CD34+ CD38- cells. In mice, the level of amphoR mRNA in HSC from the bone marrow (BM) of mice treated with stem cell factor and granulocyte-colony stimulating factor was 2.8- to 7.8-fold higher than in HSC from the BM of untreated mice. These findings suggest that HSC from frozen cord blood and cytokine-mobilized BM may be superior targets for amphotropic retrovirus transduction compared with HSC from untreated adult BM.",
author = "Donald Orlic and Girard, {Laurie J.} and Anderson, {Stacie M.} and Pyle, {Louise C.} and Mervin Yoder and Hal Broxmeyer and Bodine, {David M.}",
year = "1998",
month = "5",
day = "1",
language = "English (US)",
volume = "91",
pages = "3247--3254",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "9",

}

TY - JOUR

T1 - Identification of human and mouse hematopoietic stem cell populations expressing high levels of mRNA encoding retrovirus receptors

AU - Orlic, Donald

AU - Girard, Laurie J.

AU - Anderson, Stacie M.

AU - Pyle, Louise C.

AU - Yoder, Mervin

AU - Broxmeyer, Hal

AU - Bodine, David M.

PY - 1998/5/1

Y1 - 1998/5/1

N2 - One obstacle to retrovirus-mediated gene therapy for human hematopoietic disorders is the low efficiency of gene transfer into pluripotent hematopoietic stem cells (HSC). We have previously shown a direct correlation between retrovirus receptor mRNA levels in mouse HSC and the efficiency with which they are transduced. In the present study, we assayed retrovirus receptor mRNA levels in a variety of mouse and human HSC populations to identify HSC which may be more competent for retrovirus transduction. The highest levels of amphotropic retrovirus receptor (amphoR) mRNA were found in cryopreserved human cord blood HSC. The level of amphoR mRNA in Lin- CD34+ CD38- cells isolated from frozen cord blood was 12-fold higher than the level in fresh cord blood Lin- CD34+ CD38- cells. In mice, the level of amphoR mRNA in HSC from the bone marrow (BM) of mice treated with stem cell factor and granulocyte-colony stimulating factor was 2.8- to 7.8-fold higher than in HSC from the BM of untreated mice. These findings suggest that HSC from frozen cord blood and cytokine-mobilized BM may be superior targets for amphotropic retrovirus transduction compared with HSC from untreated adult BM.

AB - One obstacle to retrovirus-mediated gene therapy for human hematopoietic disorders is the low efficiency of gene transfer into pluripotent hematopoietic stem cells (HSC). We have previously shown a direct correlation between retrovirus receptor mRNA levels in mouse HSC and the efficiency with which they are transduced. In the present study, we assayed retrovirus receptor mRNA levels in a variety of mouse and human HSC populations to identify HSC which may be more competent for retrovirus transduction. The highest levels of amphotropic retrovirus receptor (amphoR) mRNA were found in cryopreserved human cord blood HSC. The level of amphoR mRNA in Lin- CD34+ CD38- cells isolated from frozen cord blood was 12-fold higher than the level in fresh cord blood Lin- CD34+ CD38- cells. In mice, the level of amphoR mRNA in HSC from the bone marrow (BM) of mice treated with stem cell factor and granulocyte-colony stimulating factor was 2.8- to 7.8-fold higher than in HSC from the BM of untreated mice. These findings suggest that HSC from frozen cord blood and cytokine-mobilized BM may be superior targets for amphotropic retrovirus transduction compared with HSC from untreated adult BM.

UR - http://www.scopus.com/inward/record.url?scp=0032079507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032079507&partnerID=8YFLogxK

M3 - Article

C2 - 9558380

AN - SCOPUS:0032079507

VL - 91

SP - 3247

EP - 3254

JO - Blood

JF - Blood

SN - 0006-4971

IS - 9

ER -