Gene therapy in lung transplantation: Effective gene transfer via the airways

A. Jeppsson, R. Lee, C. Pellegrini, T. O'Brien, H. D. Tazelaar, C. G.A. McGregor

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objectives: Gene therapy may provide a means of modifying factors that contribute to the development of pathologic processes in transplanted lungs. Experiments were designed to study the feasibility of adenovirus-mediated gene transfer by way of the airways to the transplanted lung. Methods: Orthotopic left lung transplantation (Lewis to Lewis rats) was performed on four groups of animals. 300 μl of adenovirus solution encoding for β- galactosidase was infused into the left bronchus of donor rats at viral concentrations of 108 pfu/ml (n = 5), 109 pfu/ml (n = 6), and 1010 pfu/ml (n = 6), and the lung was ventilated for 5 minutes. Controls (n = 6) received medium only. Seven days after transplantation, native and transduced, transplanted lungs were harvested. Sections of lung were fixed and stained with a solution of X-Gal (5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside) and staining was evaluated for distribution by cell type and intensity. Results: β-Galactosidase expression was absent in the control group and in the native lungs. Two of five lungs in the 108 group expressed β- galactosidase, but in a limited distribution and intensity. All six lungs in the 109 group and five of six lungs in the 1010 group expressed β- galactosidase. The distribution and intensity of β-galactosidase expression ranged from only a few cells staining per slide to up to 75%. Pneumocytes were the most frequently stained cell type followed by alveolar macrophages. Conclusions: Gene transfer to the transplanted lung via the bronchial route is feasible and offers a novel technique to modify pathologic processes in the transplanted lung.

Original languageEnglish (US)
Pages (from-to)638-643
Number of pages6
JournalJournal of Thoracic and Cardiovascular Surgery
Volume115
Issue number3
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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    Jeppsson, A., Lee, R., Pellegrini, C., O'Brien, T., Tazelaar, H. D., & McGregor, C. G. A. (1998). Gene therapy in lung transplantation: Effective gene transfer via the airways. Journal of Thoracic and Cardiovascular Surgery, 115(3), 638-643. https://doi.org/10.1016/S0022-5223(98)70329-0