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Reconstitution of tracheal grafts with a genetically modified epithelium
Journal article   Open access   Peer reviewed

Reconstitution of tracheal grafts with a genetically modified epithelium

J F Engelhardt, E D Allen and J M Wilson
Proceedings of the National Academy of Sciences - PNAS, Vol.88(24), pp.11192-11196
12/15/1991
DOI: 10.1073/pnas.88.24.11192
PMCID: PMC53100
PMID: 1763032
url
https://europepmc.org/articles/pmc53100View
Published (Version of record) Open Access

Abstract

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.
Immunohistochemistry Transfection 3T3 Cells Actins - genetics Animals beta-Galactosidase - genetics beta-Galactosidase - metabolism Cells, Cultured Chickens Epithelial Cells Epithelium - enzymology Epithelium - ultrastructure Genetic Vectors Male Mice Microscopy, Electron Promoter Regions, Genetic Rabbits Rats Rats, Inbred F344 Receptors, LDL - genetics Repetitive Sequences, Nucleic Acid Retroviridae - genetics Trachea - cytology Trachea - transplantation

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