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Original Research: Transplantation |

Safety and Tolerability of Alveolar Type II Cell Transplantation in Idiopathic Pulmonary Fibrosis

Anna Serrano-Mollar, PhD; Gemma Gay-Jordi, PhD; Raquel Guillamat-Prats, PhD; Daniel Closa, PhD; Fernanda Hernandez-Gonzalez, MD; Pedro Marin, PhD; Felip Burgos, PhD; Jaume Martorell, PhD; Marcelo Sánchez, MD; Pedro Arguis, MD; Dolors Soy, PhD; José M. Bayas, PhD; José Ramirez, PhD; Teresa D. Tetley, PhD; Laureano Molins, PhD; Jordi Puig de la Bellacasa, PhD; Camino Rodríguez-Villar, PhD; Irene Rovira, PhD; Juan José Fiblà, MD; Antoni Xaubet, PhD
Author and Funding Information

Anna Serrano-Mollar and Antoni Xaubet contributed equally to this article as first author and also as senior author. Anna Serrano-Mollar and Antoni Xaubet share both authorships.

FUNDING/SUPPORT: This work was supported by grants from Fundación Genoma España, Consejo Superior de Investigaciones Científicas (CSIC), Ministerio de Sanidad Política Social e Igualdad (TRA-020 and EC-10-89), Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (PI12/01122 and PI13/00282), “Cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, Una manera de hacer Europa,” and Fundació la Marató de TV3 (MTV3 122410).

aDepartamento de Patología Experimental, Instituto de Investigaciones Biomédicas de Barcelona IIBB- CSIC Barcelona, Spain

bCentro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain

cServicio de Neumología, Hospital Clínic, Barcelona, Spain

dServicio de Inmunología, Hospital Clínic, Barcelona, Spain

eDepartamento de Radiología, Hospital Clínic, Barcelona, Spain

fServicio de Medicina Preventiva y Epidemiología, Hospital Clínic, Barcelona, Spain

gServicio de Anatomía Patológica, Hospital Clínic, Barcelona, Spain

hServicio de Cirugía Torácica, Hospital Clínic, Barcelona, Spain

iServicio de Microbiología, Hospital Clínic, Barcelona, Spain

jUnidad de Donación, Hospital Clínic, Barcelona, Spain

kServicio de Anestesiología y Reanimación, Hospital Clínic, Barcelona, Spain

lFacultad de Medicina, Universidad de Barcelona, Barcelona, Spain

mServicio de Cirugía Torácica, Hospital Universitario Sagrat Cor, Barcelona, Spain

nSection of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London

CORRESPONDENCE TO: Anna Serrano-Mollar, PhD, Department of Experimental Pathology, IIBB-CSIC, Rosselló, 161, 7a, 08036 Barcelona, Spain


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(3):533-543. doi:10.1016/j.chest.2016.03.021
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Background  Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited response to currently available therapies. Alveolar type II (ATII) cells act as progenitor cells in the adult lung, contributing to alveolar repair during pulmonary injury. However, in IPF, ATII cells die and are replaced by fibroblasts and myofibroblasts. In previous preclinical studies, we demonstrated that ATII-cell intratracheal transplantation was able to reduce pulmonary fibrosis. The main objective of this study was to investigate the safety and tolerability of ATII-cell intratracheal transplantation in patients with IPF.

Methods  We enrolled 16 patients with moderate and progressive IPF who underwent ATII-cell intratracheal transplantation through fiberoptic bronchoscopy. We evaluated the safety and tolerability of ATII-cell transplantation by assessing the emergent adverse side effects that appeared within 12 months. Moreover, pulmonary function, respiratory symptoms, and disease extent during 12 months of follow-up were evaluated.

Results  No significant adverse events were associated with the ATII-cell intratracheal transplantation. After 12 months of follow-up, there was no deterioration in pulmonary function, respiratory symptoms, or disease extent.

Conclusions  Our results support the hypothesis that ATII-cell intratracheal transplantation is safe and well tolerated in patients with IPF. This study opens the door to designing a clinical trial to elucidate the potential beneficial effects of ATII-cell therapy in IPF.

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