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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 C. Yoder,
Hal E. Broxmeyer, and
David M. Bodine
From the Hematopoiesis Section, Laboratory of Gene Transfer, National
Human Genome Research Institute (NHGRI), National Institutes of Health
(NIH), Bethesda, MD; the Department of Pediatrics, Riley Hospital for
Children; the Departments of Microbiology/Immunology and Medicine; and
the Walther Oncology Center, Indiana University School of Medicine,
Indianapolis, IN.
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.
Blood, Vol. 91 No. 9 (May 1), 1998:
pp. 3247-3254
© 1998 by The American Society of Hematology.
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