Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Dec 15;88(24):11192–11196. doi: 10.1073/pnas.88.24.11192

Reconstitution of tracheal grafts with a genetically modified epithelium.

J F Engelhardt 1, E D Allen 1, J M Wilson 1
PMCID: PMC53100  PMID: 1763032

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.

Full text

PDF
11193

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson M. P., Rich D. P., Gregory R. J., Smith A. E., Welsh M. J. Generation of cAMP-activated chloride currents by expression of CFTR. Science. 1991 Feb 8;251(4994):679–682. doi: 10.1126/science.1704151. [DOI] [PubMed] [Google Scholar]
  2. Breuer R., Zajicek G., Christensen T. G., Lucey E. C., Snider G. L. Cell kinetics of normal adult hamster bronchial epithelium in the steady state. Am J Respir Cell Mol Biol. 1990 Jan;2(1):51–58. doi: 10.1165/ajrcmb/2.1.51. [DOI] [PubMed] [Google Scholar]
  3. Danos O., Mulligan R. C. Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6460–6464. doi: 10.1073/pnas.85.17.6460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Donnelly G. M., Haack D. G., Heird C. S. Tracheal epithelium: cell kinetics and differentiation in normal rat tissue. Cell Tissue Kinet. 1982 Mar;15(2):119–130. doi: 10.1111/j.1365-2184.1982.tb01030.x. [DOI] [PubMed] [Google Scholar]
  5. Drumm M. L., Pope H. A., Cliff W. H., Rommens J. M., Marvin S. A., Tsui L. C., Collins F. S., Frizzell R. A., Wilson J. M. Correction of the cystic fibrosis defect in vitro by retrovirus-mediated gene transfer. Cell. 1990 Sep 21;62(6):1227–1233. doi: 10.1016/0092-8674(90)90398-x. [DOI] [PubMed] [Google Scholar]
  6. Inayama Y., Hook G. E., Brody A. R., Cameron G. S., Jetten A. M., Gilmore L. B., Gray T., Nettesheim P. The differentiation potential of tracheal basal cells. Lab Invest. 1988 Jun;58(6):706–717. [PubMed] [Google Scholar]
  7. Jeffery P. K., Reid L. New observations of rat airway epithelium: a quantitative and electron microscopic study. J Anat. 1975 Nov;120(Pt 2):295–320. [PMC free article] [PubMed] [Google Scholar]
  8. Johnson N. F., Hubbs A. F. Epithelial progenitor cells in the rat trachea. Am J Respir Cell Mol Biol. 1990 Dec;3(6):579–585. doi: 10.1165/ajrcmb/3.6.579. [DOI] [PubMed] [Google Scholar]
  9. Kauffman S. L. Cell proliferation in the mammalian lung. Int Rev Exp Pathol. 1980;22:131–191. [PubMed] [Google Scholar]
  10. Kerem B., Rommens J. M., Buchanan J. A., Markiewicz D., Cox T. K., Chakravarti A., Buchwald M., Tsui L. C. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989 Sep 8;245(4922):1073–1080. doi: 10.1126/science.2570460. [DOI] [PubMed] [Google Scholar]
  11. Klein-Szanto A. J., Terzaghi M., Mirkin L. D., Martin D., Shiba M. Propagation of normal human epithelial cell populations using an in vivo culture system. Description and applications. Am J Pathol. 1982 Aug;108(2):231–239. [PMC free article] [PubMed] [Google Scholar]
  12. McColley S. A., Rosenstein B. J., Cutting G. R. Differences in expression of cystic fibrosis in blacks and whites. Am J Dis Child. 1991 Jan;145(1):94–97. doi: 10.1001/archpedi.1991.02160010100025. [DOI] [PubMed] [Google Scholar]
  13. Obara T., Conti C. J., Baba M., Resau J. H., Trifillis A. L., Trump B. F., Klein-Szanto A. J. Rapid detection of xenotransplanted human tissues using in situ hybridization. Am J Pathol. 1986 Mar;122(3):386–391. [PMC free article] [PubMed] [Google Scholar]
  14. Price J., Turner D., Cepko C. Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer. Proc Natl Acad Sci U S A. 1987 Jan;84(1):156–160. doi: 10.1073/pnas.84.1.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Randell S. H., Comment C. E., Ramaekers F. C., Nettesheim P. Properties of rat tracheal epithelial cells separated based on expression of cell surface alpha-galactosyl end groups. Am J Respir Cell Mol Biol. 1991 Jun;4(6):544–554. doi: 10.1165/ajrcmb/4.6.544. [DOI] [PubMed] [Google Scholar]
  16. Riordan J. R., Rommens J. M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J. L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. doi: 10.1126/science.2475911. [DOI] [PubMed] [Google Scholar]
  17. Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
  18. Terzaghi M., Nettesheim P., Williams M. L. Repopulation of denuded tracheal grafts with normal, preneoplastic, and neoplastic epithelial cell populations. Cancer Res. 1978 Dec;38(12):4546–4553. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES