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Reconstitution of Tracheal Grafts with a Genetically Modified Epithelium
John F. Engelhardt, Edward D. Allen and James M. Wilson
Proceedings of the National Academy of Sciences of the United States of America
Vol. 88, No. 24 (Dec. 15, 1991), pp. 11192-11196
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/2359210
Page Count: 5
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A rational approach to the development of gene therapies for cystic fibrosis requires a better understanding of the cellular targets for gene transfer in the airway epithelium. We have used recombinant retroviruses to study the dynamics and lineage relationships of a regenerating rat tracheal epithelium. Primary cultures of tracheal epithelial cells were exposed to lacZ-transducing retroviruses and subsequently seeded into denuded trachea that were implanted into BALB/c (nu/nu) mice. The grafts developed a fully differentiated mucociliary epithelium containing large clones of lacZ-expressing cells with virtually all cell types represented within each clone. These data are most consistent with gene transfer into a putative progenitor cell that is capable of extensive self renewal and pleuripotent development. Vector-specific variation in transgene expression was noted in the various cell types.
Proceedings of the National Academy of Sciences of the United States of America © 1991 National Academy of Sciences