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J Thorac Cardiovasc Surg 1998;115:638-643
© 1998 Mosby, Inc.

CARDIAC AND PULMONARY REPLACEMENT

Gene Therapy In Lung Transplantation: Effective Gene Transfer Via The Airways

This work was supported by the Mayo Clinic and Foundation, Rochester, Minnesota, and the Bruce and Ruth Rappaport Program in Vascular Biology. Dr Anders Jeppsson is a visiting scientist supported by grants from University of Gothenburg, Assar Gabrielsson Foundation, Swedish Medical Society, Swedish Medical Research Council and Gothenburg Medical Society.

Received for publication May 22, 1997; revisions requested July 15, 1997; revisions received August 13, 1997; accepted for publication Sept. 22, 1997. Address for reprints: C. G. A. McGregor, MB, FRCS, 6-716 Mary Brigh D, Saint Marys Hospital, Mayo Clinic, Rochester, MN 55905.

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 ß-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-ß-D-galactopyranoside) and staining was evaluated for distribution by cell type and intensity.
Results: ß-Galactosidase expression was absent in the control group and in the native lungs. Two of five lungs in the 10⁸ group expressed ß-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 ß-galactosidase. The distribution and intensity of ß-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.

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