Francesco Petrella1, Francesca Toffalorio2, Stefano Brizzola3, Tommaso Martino De Pas2, Stefania Rizzo4, Massimo Barberis5, Piergiuseppe Pelicci6, Lorenzo Spaggiari7, Fabio Acocella3. 1. Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy. Electronic address: francesco.petrella@ieo.it. 2. Division of Medical Oncology of the Respiratory Tract, European Institute of Oncology, Milan, Italy. 3. Department of Health, Animal Science and Public Health, Università degli Studi di Milano, Milan, Italy. 4. Department of Radiology, European Institute of Oncology, Milan, Italy. 5. Department of Pathology, European Institute of Oncology, Milan, Italy. 6. Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. 7. Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy.
Abstract
BACKGROUND: Bronchopleural fistula after lung resection still represents a challenging life-threatening complication for thoracic surgeons. Considering its extremely high mortality rate, an effective treatment is urgently required. Our project investigated the hypothesis of experimental bronchopleural fistula closure by bronchoscopic injection of autologous bone marrow-derived mesenchymal stem cells into the cavity of the fistula, evaluating its feasibility and safety in a large animal model. METHODS: An experimental bronchopleural fistula was created in 9 goats after right upper tracheal lobectomy. The animals were randomly assigned to two groups: one received autologous bone marrow-derived mesenchymal stem cell bronchoscopic transplantation; the other received standard bronchoscopic fibrin glue injection. RESULTS: All animals receiving bronchoscopic stem cell transplantation presented fistula closure by extraluminal fibroblast proliferation and collagenous matrix development; none (0%) died during the study period. All animals receiving standard treatment still presented bronchopleural fistula; 2 of them (40%) died. Findings were confirmed by pathology examination, computed tomography, and magnetic resonance imaging. CONCLUSIONS: Bronchoscopic transplantation of bone marrow-derived mesenchymal stem cells effectively closes experimental bronchopleural fistula by extraluminal fibroblast proliferation and collagenous matrix development. Stem cells may play a crucial role in the treatment of postresectional bronchopleural fistula after standard lung resection. Although these results provide a basis for the development of clinical therapeutic strategies, the exact mechanism by which they are obtained is not yet completely clear; further studies are required to understand exactly how stem cells work in this field.
BACKGROUND:Bronchopleural fistula after lung resection still represents a challenging life-threatening complication for thoracic surgeons. Considering its extremely high mortality rate, an effective treatment is urgently required. Our project investigated the hypothesis of experimental bronchopleural fistula closure by bronchoscopic injection of autologous bone marrow-derived mesenchymal stem cells into the cavity of the fistula, evaluating its feasibility and safety in a large animal model. METHODS: An experimental bronchopleural fistula was created in 9 goats after right upper tracheal lobectomy. The animals were randomly assigned to two groups: one received autologous bone marrow-derived mesenchymal stem cell bronchoscopic transplantation; the other received standard bronchoscopic fibrin glue injection. RESULTS: All animals receiving bronchoscopic stem cell transplantation presented fistula closure by extraluminal fibroblast proliferation and collagenous matrix development; none (0%) died during the study period. All animals receiving standard treatment still presented bronchopleural fistula; 2 of them (40%) died. Findings were confirmed by pathology examination, computed tomography, and magnetic resonance imaging. CONCLUSIONS: Bronchoscopic transplantation of bone marrow-derived mesenchymal stem cells effectively closes experimental bronchopleural fistula by extraluminal fibroblast proliferation and collagenous matrix development. Stem cells may play a crucial role in the treatment of postresectional bronchopleural fistula after standard lung resection. Although these results provide a basis for the development of clinical therapeutic strategies, the exact mechanism by which they are obtained is not yet completely clear; further studies are required to understand exactly how stem cells work in this field.
Authors: Johnathon M Aho; Allan B Dietz; Darcie J Radel; Greg W Butler; Mathew Thomas; Timothy J Nelson; Brian T Carlsen; Stephen D Cassivi; Zachary T Resch; William A Faubion; Dennis A Wigle Journal: Stem Cells Transl Med Date: 2016-06-24 Impact factor: 6.940