Anna Serrano-Mollar1, Gemma Gay-Jordi2, Raquel Guillamat-Prats2, Daniel Closa3, Fernanda Hernandez-Gonzalez2, Pedro Marin4, Felip Burgos5, Jaume Martorell6, Marcelo Sánchez7, Pedro Arguis7, Dolors Soy8, José M Bayas9, José Ramirez10, Teresa D Tetley11, Laureano Molins12, Jordi Puig de la Bellacasa13, Camino Rodríguez-Villar14, Irene Rovira15, Juan José Fiblà16, Antoni Xaubet17. 1. 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. 2. 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. 3. Departamento de Patología Experimental, Instituto de Investigaciones Biomédicas de Barcelona IIBB- CSIC Barcelona, Spain. 4. Servicio de Neumología, Hospital Clínic, Barcelona, Spain. 5. Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain. 6. Servicio de Inmunología, Hospital Clínic, Barcelona, Spain. 7. Departamento de Radiología, Hospital Clínic, Barcelona, Spain. 8. 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. 9. Servicio de Medicina Preventiva y Epidemiología, Hospital Clínic, Barcelona, Spain. 10. 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. 11. Section of Pharmacology and Toxicology, National Heart and Lung Institute, Imperial College London. 12. Servicio de Cirugía Torácica, Hospital Clínic, Barcelona, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain. 13. Servicio de Microbiología, Hospital Clínic, Barcelona, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain. 14. Unidad de Donación, Hospital Clínic, Barcelona, Spain. 15. Servicio de Anestesiología y Reanimación, Hospital Clínic, Barcelona, Spain. 16. Servicio de Cirugía Torácica, Hospital Universitario Sagrat Cor, Barcelona, Spain. 17. Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain; Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain.
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.
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.
Authors: Esther Marhuenda; Alvaro Villarino; Maria Leonor Narciso; Marta Camprubí-Rimblas; Ramon Farré; Núria Gavara; Antonio Artigas; Isaac Almendros; Jorge Otero Journal: Int J Mol Sci Date: 2022-04-28 Impact factor: 6.208
Authors: Kalpaj R Parekh; Janna Nawroth; Albert Pai; Shana M Busch; Christiana N Senger; Amy L Ryan Journal: Am J Physiol Cell Physiol Date: 2020-08-12 Impact factor: 4.249
Authors: Reinier Snetselaar; Aernoud A van Batenburg; Matthijs F M van Oosterhout; Karin M Kazemier; Suzan M Roothaan; Ton Peeters; Joanne J van der Vis; Roel Goldschmeding; Jan C Grutters; Coline H M van Moorsel Journal: PLoS One Date: 2017-12-27 Impact factor: 3.240