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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. Significance 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. This is the first‐in‐human application of an autologous mesenchymal stem cell (MSC)‐seeded matrix graft to repair a multiply recurrent postpneumonectomy bronchopleural fistula (BPF). Adipose‐derived MSCs were isolated from patient abdominal adipose tissue, expanded, and seeded onto bio‐absorbable mesh, which was surgically implanted at the BPF site. After clinical follow‐up of 1.5 years, the patient is clinically asymptomatic without evidence of recurrence or malignant degeneration of MSC populations in situ.

Adipose‐derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra‐articular joint space. Culture‐expanded human AMSCs grown in human platelet‐lysate were delivered via intra‐articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy. Treatment outcomes and safety were evaluated by assessing the general health, function, and behavior of the animals. Joint tissues were analyzed by x‐ray, magnetic resonance imaging, and histopathology. Intra‐articular AMSC therapy was well tolerated in this study. We did not observe adverse systemic reactions, nor did we find evidence of damage to intra‐articular joint tissues. Thus, the data generated in this study show a favorable safety profile for AMSCs within the joint space in support of a phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis. Stem Cells Translational Medicine 2017;6:910–922

: Adipose-derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra-articular joint space. Culture-expanded human AMSCs grown in human platelet-lysate were delivered via intra-articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy. Treatment outcomes and safety were evaluated by assessing the general health, function, and behavior of the animals. Joint tissues were analyzed by x-ray, magnetic resonance imaging, and histopathology. Intra-articular AMSC therapy was well tolerated in this study. We did not observe adverse systemic reactions, nor did we find evidence of damage to intra-articular joint tissues. Thus, the data generated in this study show a favorable safety profile for AMSCs within the joint space in support of a phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis. This safety study indicates that adipose-derived mesenchymal stem cells (AMSCs) can be safely used in cell therapies for joint degeneration. This finding supports a phase I clinical trial to evaluate the clinical utility of AMSCs in treating osteoarthritis.