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

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

Journal: Chest 2017;150(3):533-43

PMID: 27020420

Full Text on Elsevier Science View on PubMed

Abstract

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.

Address: Departamento de Patología Experimental, Instituto de Investigaciones Biomédicas de Barcelona IIBB- CSIC Barcelona, Spain; Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain. Electronic address: [email protected].; Departamento de Patología Experimental, Instituto de Investigaciones Biomédicas de Barcelona IIBB- CSIC Barcelona, Spain; Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Departamento de Patología Experimental, Instituto de Investigaciones Biomédicas de Barcelona IIBB- CSIC Barcelona, Spain.; Servicio de Neumología, Hospital Clínic, Barcelona, Spain.; Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.; Servicio de Inmunología, Hospital Clínic, Barcelona, Spain.; Departamento de Radiología, Hospital Clínic, Barcelona, Spain.; Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Departamento de Radiología, Hospital Clínic, Barcelona, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain.; Servicio de Medicina Preventiva y Epidemiología, Hospital Clínic, Barcelona, Spain.; Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Servicio de Anatomía Patológica, Hospital Clínic, Barcelona, Spain; Servicio de Cirugía Torácica, Hospital Universitario Sagrat Cor, Barcelona, Spain.; Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London.; Servicio de Cirugía Torácica, Hospital Clínic, Barcelona, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain.; Servicio de Microbiología, Hospital Clínic, Barcelona, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain.; Unidad de Donación, Hospital Clínic, Barcelona, Spain.; Servicio de Anestesiología y Reanimación, Hospital Clínic, Barcelona, Spain.; Servicio de Cirugía Torácica, Hospital Universitario Sagrat Cor, Barcelona, Spain.; Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain.

DOI: 10.1016/j.chest.2016.03.021

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MeSH Terms: Adrenal Cortex Hormones, Aged, Alveolar Epithelial Cells, Anti-Infective Agents, Bacterial Infections, Bronchoscopy, Cell Transplantation, Disease Progression, Female, Forced Expiratory Volume, Ganciclovir, Graft Rejection, Humans, Idiopathic Pulmonary Fibrosis, Immunosuppressive Agents, Leucovorin, Male, Middle Aged, Mycophenolic Acid, Mycoses, Nystatin, Pulmonary Diffusing Capacity, Tacrolimus, Trachea, Treatment Outcome, Trimethoprim, Sulfamethoxazole Drug Combination, Valganciclovir, Virus Diseases, Vital Capacity, Walk Test