Autologous mesenchymal stromal cells embedded with Tissucol Duo® for prevention of air leak after anatomical lung resection: results of a prospective phase I/II clinical trial with long-term follow-up

Abstract

Abstract BACKGROUND: Prolonged air leak (PAL) is the most frequent complication after pulmonary resection. Several measures have been described to prevent the occurrence of PAL in high-risk patients, however, the potential role of mesenchymal stem cells (MSCs) applied in the parenchymal suture line to prevent postoperative air leak in this setting has not been fully addressed. OBJECTIVE: To analyse the feasibility, safety and potential clinical efficacy of the implantation of autologous MSCs embedded in Tissucol Duo® as a prophylactic alternative to prevent postoperative prolonged air leak after pulmonary resection in high-risk patients. STUDY DESIGN: Phase I/II single-arm prospective clinical trial. METHODS: Six patients with high risk of PAL undergoing elective pulmonary resection were included. Autologous bone marrow-derived MSCs were expanded at our Good Manufacturing Practice (GMP) Facility and implanted (embedded in a Tissucol Duo® carrier) in the parenchymal suture line during pulmonary resection surgery. Patients were monitored in the early postoperative period and evaluated for possible complications or adverse reactions. In addition, all patients were followed-up to 5 years for clinical outcomes. RESULTS: The median age of patients included was 66 years (range: 55-70 years) and male/female ratio was 5/1. Autologous MSCs were expanded in five cases, in one case MSCs expansion was insufficient. There were no adverse effects related to cell implantation. Regarding efficacy, median air leak duration was 0 days (range: 0-2 days). The incidence of PAL was nil. Radiologically, only one patient presented pneumothorax in the chest x-ray at discharge. No adverse effects related to the procedure were recorded during the follow-up. CONCLUSIONS: The use of autologous MSCs for prevention of PAL in patients with high risk of PAL is feasible, safe, and potentially effective. TRIAL REGISTRATION: no. EudraCT: 2013-000535-27. Clinicaltrials.gov idenfier: NCT02045745.