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Serial transplantation of methotrexate-resistant bone marrow: protection of
murine recipients from drug toxicity by progeny of transduced stem cells
CA Corey, AD DeSilva, CA Holland and DA Williams
Department of Medicine, Massachusetts General Hospital, Boston.
Recombinant retroviral vectors have been used to transfer a variety of
genetic sequences into hematopoietic stem cells. Although transfer and
expression of foreign genetic sequences into reconstituting stem cells is
one approach to somatic gene therapy, few studies have shown long lasting
phenotypic changes in recipient mice in vivo. In this study, we show
successful transfer of a methotrexate-resistant cDNA (DHFRr) into
reconstituting hematopoietic stem cells using a retroviral vector, FrDHFRr,
in which the DHFR cDNA is expressed off a hybrid Friend/Moloney long term
repeat. Both primary and secondary recipients transplanted with bone marrow
cells infected with this recombinant retrovirus show improved survival and
protection from methotrexate- induced marrow toxicity when compared with
control animals. These data suggest that retroviral-mediated gene transfer
of DHFRr cDNA leads to a stable change in the phenotype of hematopoietic
stem cells and progeny derived from those cells in vivo after bone marrow
transplantation. Gene transfer using recombinant retroviral vectors seems
to be one rational approach to establishing chemotherapy-resistant bone
marrow cells.
Volume 75,
Issue 2,
pp. 337-343,
01/15/1990
Copyright © 1990 by The American Society of Hematology
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