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PG Eipers, JC Krauss, BO Palsson, SG Emerson, RF Todd and MF Clarke
Department of Internal Medicine, University of Michigan, Ann Arbor
48109-0668, USA.
Hematopoietic stem cell gene therapy holds the promise of being able to
treat a variety of inherited and acquired diseases of the hematopoietic
stem cell. However, to date, genetic modification of the human
hematopoietic stem cell has been relatively inefficient. Here, we report
the results of using a bioreactor system to expand hematopoietic cells
after a brief retrovirus infection using a high titer, replication
defective virus encoding for murine CD18. The retrovirus transduced culture
continued to produce genetically modified hematopoietic progenitors for up
to 6 weeks, the duration of the culture period. Up to one-third of the
long-term culture initiating cell (LTC-IC) are genetically modified by the
culture conditions. Murine CD18 can be expressed on the cell surface of up
to 20% of the mature cells generated by the culture system, suggesting that
clinically significant levels of gene transfer may be occurring. These
results demonstrate the feasibility of using continuous perfusion
bioreactors as a method of efficiently modifying human hematopoietic stem
cells.
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| Copyright © 1995 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||