title: Safety and Tolerability of Alveolar Type II Cell Transplantation in Idiopathic Pulmonary Fibrosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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: anna.serranomollar@iibb.csic.es.
authors.forename: Anna
authors.initials: A
authors.lastname: Serrano-Mollar
authors.affiliation: 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.
authors.forename: Gemma
authors.initials: G
authors.lastname: Gay-Jordi
authors.affiliation: 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.
authors.forename: Raquel
authors.initials: R
authors.lastname: Guillamat-Prats
authors.affiliation: Departamento de Patología Experimental, Instituto de Investigaciones Biomédicas de Barcelona IIBB- CSIC Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Closa
authors.affiliation: 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.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Hernandez-Gonzalez
authors.affiliation: Servicio de Neumología, Hospital Clínic, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Marin
authors.affiliation: Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Felip
authors.initials: F
authors.lastname: Burgos
authors.affiliation: Servicio de Inmunología, Hospital Clínic, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Martorell
authors.affiliation: Departamento de Radiología, Hospital Clínic, Barcelona, Spain.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Sánchez
authors.affiliation: Departamento de Radiología, Hospital Clínic, Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Arguis
authors.affiliation: 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.
authors.forename: Dolors
authors.initials: D
authors.lastname: Soy
authors.affiliation: Servicio de Medicina Preventiva y Epidemiología, Hospital Clínic, Barcelona, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Bayas
authors.affiliation: 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.
authors.forename: José
authors.initials: J
authors.lastname: Ramirez
authors.affiliation: Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London.
authors.forename: Teresa D
authors.initials: TD
authors.lastname: Tetley
authors.affiliation: Servicio de Cirugía Torácica, Hospital Clínic, Barcelona, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain.
authors.forename: Laureano
authors.initials: L
authors.lastname: Molins
authors.affiliation: Servicio de Microbiología, Hospital Clínic, Barcelona, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain.
authors.forename: Jordi Puig
authors.initials: JP
authors.lastname: de la Bellacasa
authors.affiliation: Unidad de Donación, Hospital Clínic, Barcelona, Spain.
authors.forename: Camino
authors.initials: C
authors.lastname: Rodríguez-Villar
authors.affiliation: Servicio de Anestesiología y Reanimación, Hospital Clínic, Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Rovira
authors.affiliation: Servicio de Cirugía Torácica, Hospital Universitario Sagrat Cor, Barcelona, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Fiblà
authors.affiliation: Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Xaubet
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D056809:Alveolar Epithelial Cells / Q000637:transplantation*; D000890:Anti-Infective Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000517:prevention & control; D001999:Bronchoscopy; D017690:Cell Transplantation / Q000379:methods*; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000627:therapeutic use; D009181:Mycoses / Q000517:prevention & control; D009761:Nystatin / Q000627:therapeutic use; D011653:Pulmonary Diffusing Capacity; D016559:Tacrolimus / Q000627:therapeutic use; D014132:Trachea; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D000077562:Valganciclovir; D014777:Virus Diseases / Q000517:prevention & control; D014797:Vital Capacity; D000070857:Walk Test
chemical_list: D000305:Adrenal Cortex Hormones; D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents; D009761:Nystatin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D000077562:Valganciclovir; D009173:Mycophenolic Acid; D015774:Ganciclovir; D002955:Leucovorin; D016559:Tacrolimus
keywords: alveolar type II cells; cell therapy; idiopathic pulmonary fibrosis