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Intratracheal Transplantation of Alveolar Type II Cells Reverses Bleomycin-induced Lung Fibrosis

¹ Department of Experimental Pathology, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain; ² Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias, Barcelona, Spain; and ³ Servei de Pneumologia, Institut Clínic del Tórax, Hospital Clínic, Barcelona, Spain

Correspondence and requests for reprints should be addressed to Anna Serrano-Mollar, Ph.D., Department of Experimental Pathology, IIBB-CSIC-IDIBAPS, C/Rosselló, 161, 7^a, 08036 Barcelona, Spain. E-mail: amsbam{at}iibb.csic.es

Rationale: Transplantation of stem cells has been proposed as a strategy for repair of lung fibrosis. Nevertheless, many studies have yielded controversial results that currently limit the potential use of these cells as an efficient treatment. Alveolar type II cells are the progenitor cells of the pulmonary epithelium and usually proliferate after epithelial cell injury. During lung fibrosis, however, the altered regeneration process leads to uncontrolled fibroblast proliferation.

Objectives: To investigate whether intratracheal transplantation of isolated alveolar type II cells can halt and reverse the fibrotic process in an experimental model of bleomycin-induced lung fibrosis in rats.

Methods: Lung fibrosis was induced in syngeneic female Lewis rats by a single intratracheal instillation of bleomycin (2.5 U/kg). Animals were transplanted with alveolar type II cells from male animals at a dose of 2.5 x 10⁶ cells per animal 3, 7, and 15 days after endotracheal bleomycin instillation. Animals were killed 21 days after the induction of lung fibrosis.

Measurements and Main Results: Lung fibrosis was assessed by histologic study and determination of hydroxyproline content. Engraftment of transplanted cells was measured by real-time polymerase chain reaction for the Y chromosome and by fluorescence in situ hybridization for the Y chromosome. Transplantation of alveolar type II cells into damaged lung 3, 7, or 15 days after bleomycin instillation led to reduced collagen deposition, and reduction in the severity of pulmonary fibrosis.

Conclusions: This study demonstrates the potential role of alveolar type II cell transplantation in designing future therapies for lung fibrosis.

Key Words: cell therapy • lung epithelium • lung repair

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Idiopathic pulmonary fibrosis is a fibroproliferative disorder characterized histopathologically by heterogeneous interstitial fibrosis with fibroblastic foci and honeycomb lung. At present no treatment has proven beneficial to survival. What This Study Adds to the Field Transplantation of alveolar type II cells is successful in reversing lung fibrosis in the experimental bleomycin model in rats.

 

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