title: Closure of a Recurrent Bronchopleural Fistula Using a Matrix Seeded With Patient-Derived Mesenchymal Stem Cells.
abstract: : Management of recurrent bronchopleural fistula (BPF) after pneumonectomy remains a challenge. Although a variety of devices and techniques have been described, definitive management usually involves closure of the fistula tract through surgical intervention. Standard surgical approaches for BPF incur significant morbidity and mortality and are not reliably or uniformly successful. We describe the first-in-human application of an autologous mesenchymal stem cell (MSC)-seeded matrix graft to repair a multiply recurrent postpneumonectomy BPF. Adipose-derived MSCs were isolated from patient abdominal adipose tissue, expanded, and seeded onto bio-absorbable mesh, which was surgically implanted at the site of BPF. Clinical follow-up and postprocedural radiological and bronchoscopic imaging were performed to ensure BPF closure, and in vitro stemness characterization of patient-specific MSCs was performed. The patient remained clinically asymptomatic without evidence of recurrence on bronchoscopy at 3 months, computed tomographic imaging at 16 months, and clinical follow-up of 1.5 years. There is no evidence of malignant degeneration of MSC populations in situ, and the patient-derived MSCs were capable of differentiating into adipocytes, chondrocytes, and osteocytes using established protocols. Isolation and expansion of autologous MSCs derived from patients in a malnourished, deconditioned state is possible. Successful closure and safety data for this approach suggest the potential for an expanded study of the role of autologous MSCs in regenerative surgical applications for BPF.
  
  
  
  Bronchopleural fistula is a severe complication of pulmonary resection. Current management is not reliably successful. This work describes the first-in-human application of an autologous mesenchymal stem cell (MSC)-seeded matrix graft to the repair of a large, multiply recurrent postpneumonectomy BPF. Clinical follow-up of 1.5 years without recurrence suggests initial safety and feasibility of this approach. Further assessment of MSC grafts in these difficult clinical scenarios requires expanded study.
authors.affiliation: Division of General Thoracic Surgery, Mayo Clinic, Rochester, Minnesota, USA Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Johnathon M
authors.initials: JM
authors.lastname: Aho
authors.affiliation: Human Cell Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Dietz
authors.affiliation: Human Cell Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Darcie J
authors.initials: DJ
authors.lastname: Radel
authors.affiliation: Human Cell Therapy Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Greg W
authors.initials: GW
authors.lastname: Butler
authors.affiliation: Cardiothoracic Surgery, Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Mathew
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Division of General Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Nelson
authors.affiliation: Division of Plastic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Carlsen
authors.affiliation: Division of General Thoracic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Cassivi
authors.affiliation: Center for Regenerative Medicine Biotrust, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Resch
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Faubion
authors.affiliation: Division of General Thoracic Surgery, Mayo Clinic, Rochester, Minnesota, USA wigle.dennis@mayo.edu.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Wigle
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D001983:Bronchial Fistula / Q000209:etiology / Q000628:therapy*; D005260:Female; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D010995:Pleural Diseases / Q000209:etiology / Q000628:therapy; D011013:Pneumonectomy / Q000009:adverse effects; D011183:Postoperative Complications / Q000628:therapy
keywords: Bronchopleural fistula; Cell transplantation; Cellular therapy; Clinical translation; Mesenchymal stem cells; Stem cell transplantation