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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3210-3217
From the Department of Molecular Genetics and Microbiology,
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson
Medical School; and the Graduate Program in Microbiology and Molecular
Genetics, Rutgers University, Piscataway, NJ.
The current paradigm concerning the kinetics of hematopoiesis is
that only the most primitive pluripotential bone marrow stem cells can
support prolonged hematopoiesis whereas more differentiated, lineage-committed stem cells can only contribute to a particular lineage for a limited period of time. In this study, we present evidence that in mice, the spleen contains a long-lived
myeloid-committed stem cell population(s) that continuously replenishes
the mature myeloid lineage for at least 9 months. After
myeloid-specific retroviral-mediated gene transfer, the exogenous gene
could be detected in thioglycollate-induced macrophages and
granulocytes by Southern blot analysis and by in situ polymerase chain
reaction on an individual cell basis. The targeted stem cell population does not repopulate the bone marrow in secondary recipients and did not
give rise to cells other than cells of the myeloid lineage. It
therefore represents the first nonpluripotential stem cell population
capable of replenishing a hemopoietic lineage for a long period of
time. The ability to target a myeloid-specific stem cell could
facilitate gene therapy of congenital disorders of the myeloid system
such as lysosomal storage diseases. It also offers a unique opportunity
to assess the immunologic consequences of expressing an exogenous gene
of choice exclusively in the myeloid lineage.
© 1998 by The American Society of Hematology.
This article has been cited by other articles:
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| Copyright © 1998 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
