Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis

Abstract

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 10(6) 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.