Adipose-Derived CellsNovel bronchoscopic treatment for bronchopleural fistula using adipose-derived stromal cells
Introduction
Bronchopleural fistula (BPF), a communication between the pleural space and bronchial tree, is a rare and potentially fatal complication that usually results from surgical procedures involving pulmonary resection. The reported incidence of BPF varies between 1.5% and 28% after pneumonectomy and 0.5% after lobectomy [1].
Management of BPF is still a therapeutic challenge because of a lack of scientific evidence [2]. Therapeutic options range from conservative treatment to aggressive surgical procedures, which are sometimes disabling. In recent decades, flexible bronchoscopy has gained acceptance as a diagnostic and therapeutic modality for patients with BPF, especially for high-risk surgical patients [3]. Multiple biological and artificial compounds have been applied through bronchoscopy, with varying degrees of success [3], [4]. However, further studies are needed to elucidate the most effective sealant and the therapeutic approach that produces the most favorable patient outcomes.
Current studies have suggested that adult stem cells could participate in regenerating and repairing diseased airways and lungs [5], [6], [7], [8]. We have previously reported the potential application of adipose-derived mesenchymal stromal cells (ASCs) in the management of fistulous pathology of the airways and digestive system [9], [10]. In light of our clinical experience, we developed a minimally invasive bronchoscopic treatment of BPF, using ASCs. The therapeutic protocol for the use of stromal vascular fraction of adipose tissue (SVF) was presented to and approved by the authorities of the La Paz University Hospital and the Spanish health authorities, and the patients signed the consent for treatment and for the publication of the results in scientific journals and congresses within the anonymity, according to the requirements of Spanish law and Declaration of Helsinki. The patients signed a detailed informed consent form prior to the procedure, and they were informed of the procedure by surgical team.
Section snippets
Isolation and characterization of autologous ASCs
We used cells from SVF of 80 to 100 mL of lipo-aspirate, that is, ASCs without expansion. To extract the cellular fraction, the washed fat was digested with type I collagenase (GIBCO BRL) at a final concentration of 0.075% in saline solution at 37°C for 45 min. Collagenase was inactivated and tissue disaggregate were then centrifuged for 10 min at 250 g, and phosphate-buffered saline was used again to wash the pellet. Centrifugation was repeated, and the remaining erythrocytes were lysed. To
Results
In all cases, cell viability was higher than 92%. Adherent cells were characterized from 10% of SVF. Cells were cultured and adherent cells were analyzed by flow cytometry, which revealed 2 weeks after isolation that they were positive for CD29, CD44, CD90 and CD105 and negative for CD11b, CD34 and CD133, thus confirming their mesenchymal phenotype (data not shown).
In patient 1, two bronchoscopic interventions were necessary to achieve complete fistula closure. In the first procedure, we used
Discussion
Pulmonary surgical procedures remain the leading cause of BPFs, which are associated with increased morbidity and mortality, prolonged hospital stays and high resource usage [1], [2], [3]. BPF It is a rare condition, and, in our hospital, we have only treated two cases during these 2 years of study duration. Despite advances in surgical techniques and perioperative care, BPF management remains a challenge. Current treatment options for BPF include a range of surgical and medical procedures and,
Acknowledgments
The authors gratefully acknowledge the support of the Thoracic Surgery and Anesthesiology Departments of their hospital and in particular the Bronchoscopy Unit. They also thank Oliver Shaw (IIS-FJD) for revising the manuscript for aspects related to the English language. This study was funded by the Spanish Ministry of Health and Consumer Affairs (via a cooperative network for cell therapy research [TerCel RD12-0019-0035]-FEDER) and a grant from the Spanish Health Research Fund (EC11-212).
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