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 Citations (Scopus)

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 - 1998

Fingerprint

Lung Transplantation
Genetic Therapy
Galactosidases
Lung
Genes
Pathologic Processes
Adenoviridae
Staining and Labeling
Alveolar Epithelial Cells
Alveolar Macrophages
Feasibility Studies
Bronchi
Galactose
Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

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

Gene therapy in lung transplantation : Effective gene transfer via the airways. / Jeppsson, A.; Lee, R.; Pellegrini, C.; O'Brien, T.; Tazelaar, H. D.; McGregor, C. G A.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 115, No. 3, 1998, p. 638-643.

Research output: Contribution to journalArticle

Jeppsson, A, Lee, R, Pellegrini, C, O'Brien, T, Tazelaar, HD & McGregor, CGA 1998, 'Gene therapy in lung transplantation: Effective gene transfer via the airways', Journal of Thoracic and Cardiovascular Surgery, vol. 115, no. 3, pp. 638-643. https://doi.org/10.1016/S0022-5223(98)70329-0
Jeppsson, A. ; Lee, R. ; Pellegrini, C. ; O'Brien, T. ; Tazelaar, H. D. ; McGregor, C. G A. / Gene therapy in lung transplantation : Effective gene transfer via the airways. In: Journal of Thoracic and Cardiovascular Surgery. 1998 ; Vol. 115, No. 3. pp. 638-643.
@article{3ee8dffbbba74570805edc897e2076ac,
title = "Gene therapy in lung transplantation: Effective gene transfer via the airways",
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.",
author = "A. Jeppsson and R. Lee and C. Pellegrini and T. O'Brien and Tazelaar, {H. D.} and McGregor, {C. G A}",
year = "1998",
doi = "10.1016/S0022-5223(98)70329-0",
language = "English (US)",
volume = "115",
pages = "638--643",
journal = "Journal of Thoracic and Cardiovascular Surgery",
issn = "0022-5223",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Gene therapy in lung transplantation

T2 - Effective gene transfer via the airways

AU - Jeppsson, A.

AU - Lee, R.

AU - Pellegrini, C.

AU - O'Brien, T.

AU - Tazelaar, H. D.

AU - McGregor, C. G A

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0031892950&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031892950&partnerID=8YFLogxK

U2 - 10.1016/S0022-5223(98)70329-0

DO - 10.1016/S0022-5223(98)70329-0

M3 - Article

C2 - 9535452

AN - SCOPUS:0031892950

VL - 115

SP - 638

EP - 643

JO - Journal of Thoracic and Cardiovascular Surgery

JF - Journal of Thoracic and Cardiovascular Surgery

SN - 0022-5223

IS - 3

ER -