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

[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 th...

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Autores: Serrano-Mollar, Anna, Nácher, María, Gay-Jordi, Gemma, Closa, Daniel, Xaubet, Antoni, Bulbena, Oriol
Tipo de recurso: artículo
Fecha de publicación:2007
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/89389
Acceso en línea:http://hdl.handle.net/10261/89389
Access Level:acceso abierto
Palabra clave:Lung epithelium
Cell therapies
Lung repair
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spelling Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosisSerrano-Mollar, AnnaNácher, MaríaGay-Jordi, GemmaClosa, DanielXaubet, AntoniBulbena, OriolLung epitheliumCell therapiesLung repair[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 × 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 anddetermination 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.Supported by grant FIS PI060679 from the Spanish Ministry of Health and by grant N-2005-79 from the Sociedad Española de Neumología y Cirugía Torácica (SEPAR).Peer ReviewedAmerican Thoracic Society2014201420072014info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/89389reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1164/rccm.200610-1491OCinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/893892026-05-22T06:33:51Z
dc.title.none.fl_str_mv Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis
title Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis
spellingShingle Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis
Serrano-Mollar, Anna
Lung epithelium
Cell therapies
Lung repair
title_short Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis
title_full Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis
title_fullStr Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis
title_full_unstemmed Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis
title_sort Intratracheal transplantation of alveolar type II cells reverses bleomycin-induced lung fibrosis
dc.creator.none.fl_str_mv Serrano-Mollar, Anna
Nácher, María
Gay-Jordi, Gemma
Closa, Daniel
Xaubet, Antoni
Bulbena, Oriol
author Serrano-Mollar, Anna
author_facet Serrano-Mollar, Anna
Nácher, María
Gay-Jordi, Gemma
Closa, Daniel
Xaubet, Antoni
Bulbena, Oriol
author_role author
author2 Nácher, María
Gay-Jordi, Gemma
Closa, Daniel
Xaubet, Antoni
Bulbena, Oriol
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Lung epithelium
Cell therapies
Lung repair
topic Lung epithelium
Cell therapies
Lung repair
description [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 × 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 anddetermination 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.
publishDate 2007
dc.date.none.fl_str_mv 2007
2014
2014
2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/89389
url http://hdl.handle.net/10261/89389
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1164/rccm.200610-1491OC
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Thoracic Society
publisher.none.fl_str_mv American Thoracic Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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