Elsevier

Cytotherapy

Volume 18, Issue 1, January 2016, Pages 36-40
Cytotherapy

Adipose-Derived Cells
Novel bronchoscopic treatment for bronchopleural fistula using adipose-derived stromal cells

https://doi.org/10.1016/j.jcyt.2015.10.003Get rights and content

Abstract

Background aims

In this report, we describe the successful bronchoscopic management of bronchopleural fistula in two patients, using autologous adipose-derived stromal cells. Cell therapy was considered for 2 cases of bronchopleural fistula refractory to conventional surgical treatment after control of the primary disease was confirmed and active pleural infection was ruled out. Briefly, adipose-derived stem cells were first isolated from lipoaspirate and used without cell expansion. In 24 months, we have not received more patients with bronchopleural fistula in our hospital and we have not been able to include more patients.

Methods

Briefly, adipose-derived stem cells were first isolated from lipo-aspirate and used without cell expansion. A bronchopleural fistula was identified through bronchoscopy, and the mucosa surrounding the fistula was ablated with an argon plasma coagulator. Isolated stem cells were then endoscopically injected into the de-epithelialized area and fistulous tract. If an open thoracostomy was present at the time of the intervention, the same procedure was performed on the pleural side. Bronchoscopic follow-up was scheduled weekly during the first month, monthly during the first year, and then yearly. The underlying etiologies were left pneumonectomy and right lower video-assisted lobectomy for non–small-cell lung cancer. The sizes of the fistulas were 6 mm and 3 mm in diameter, respectively.

Results

Both patients were discharged on the first postoperative day. The 3-year follow-up revealed a successful and maintained fistula closure, no treatment-related adverse reactions, nonlocal malignant recurrence and improved quality of life.

Conclusions

This preliminary study showed that bronchoscopic application of autologous adipose-derived stem cells is a feasible, safe and effective procedure for treating bronchopleural fistula.

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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