Endobronchial autologous bone marrow-mesenchymal stromal cells in idiopathic pulmonary fibrosis (phase I)

RationaleIdiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells have shown benefit in other inflammatory diseases.ObjectivesEvaluate the safety and feasibility of endobronchial administration of bone marrow autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF.MethodsA phase-I multicenter clinical Trial (ClinicalTrials.gov:NCT01919827) with a single endobronchial administration of autologous adult BM-MSC in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, 3 patients will be included sequentially in 3 dose cohorts (10×10^6, 50×10^6, and 100×10^6 cells). In a second phase, 9 patients will receive the highest tolerated dose. Follow-up with PFT, 6MWT, and SGRQ were done at 1, 2, 3, 6, and 12 months, and with a computed tomography at 3, 6, and 12 months.FindingsTwenty-one bone marrow samples were obtained from 17 patients. Three patients were excluded for treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSCs infusion. No treatment related severe adverse events were observed during follow-up. Compared to baseline, the mean FVC showed an initial decline of 8.1% at three months. The number of patients without functional progression was 6 (46%) at 3 months and 3 (23%) at 12 months.ConclusionsThe endobronchial infusion of BM-MSCs did not cause immediate serious adverse events in IPF patients, but a relevant proportion of patients suffered clinical and/or functional progression. Genomic instability of BM-MSCs during culture found in three patients may be troublesome for the use of autologous MSCs in IPF patients.

FIRST EXPERIENCE OF CELL TECHNOLOGIES IN THORACIC SURGERY

Bronchoscopic bronchial fistulas closing tactics, despite the merits, is not sufficiently developed and is of limited use. One of the new ways of improving this area may consist of endobronchial bronchus occlusion of the fistula using cellular technology. The purpose of this study was to evaluate the effectiveness of endoscopic treatment of postoperative bronchial fistulas using cultured allogeneic fibroblasts. The study included 10 patients with bronchopleural fistula after pneumonectomy transferred for lung cancer and infectious and destructive process. The diameter of the defect bronchial stump averaged 5 mm. Endobronchial intervention consisted of submucosal injection of a suspension allofibroblastov human bronchial stump fistula zone. Introduction of cell suspension was carried out in an isotonic saline submucosal fistula bronchus area 2-5 points total volume of 1.5 ml. Concentration allofibroblastov - 3 x 10 6 cells / ml. State of bronchial stump and residual pleural cavity to monitor the implementation of bronchoscopy, chest X-ray, CT scan. It is shown that after endobronchial administration fibroblast suspension clearance fistula was not detected in 6 cases out of 10. obturation of the lumen of the bronchus occurs within 7-9 days after cell transplantation. In the remaining patients fistula persisted, requiring re-cellular infiltration. Follow-up bronchoscopy in two cases the fistula ended blindly and do not communicate with the pleural cavity, the diameter of the fistula opening in two patients decreased significantly, but not completely closed. Thus, bronhoendoskopic submucosal administration of a suspension allofibroblasts in projection bronchial fistula should be considered as a promising method of conservative treatment failure bronchial stump after radical operations on the lungs, allowing 60-80% of cases, to avoid re-open surgery.

PHARMACOLOGICAL AUGMENTATION OF LUNG RECRUITMENT EFFECTS LN THE THERAPY OF ACUTE RESPIRATORY DISTRESSSYNDROME AFTER CARDIAC SURGERY

The aim. To estimate efficacious of combined application of lung recruitment maneuver (LR) and surfactant administration for the treatment of ARDS after cardiac surgery. Materials and methods. 33 cardiac surgery patients with ARDS were included in to prospective, controlled non-randomized study. LR technique was used in 14 patients, who were included into the "LR" group. In 19 cases LR were combined with endobronchial administration of surfactant (Surfactant-BL, ”Biosurf” Russia), these patients were included into the "LR and surfactant" group. Results. Significant difference from baseline FiO 2 observed after 12 h in "LR and surfactant" group and after 24 h in "LR" group. Significant decrease from the baseline PEEP was observed after 48 h in "LR and surfactant" group and after 72 h in "LR" group. The duration of respiratory support was shorter in the "LR and surfactant" group: 87,5 ± 35,3 h vs 175,3 ± 52,5, p <0,001. There was significant difference in the incidences of ventilator-associated pneumonia (VAP): 10.5% in the "LR and surfactant" group and 42.9% in the "LR" group, p <0,05. Furthermore, we found significant difference in the ICU stay period between groups: 132,5 ± 42,2 h in the "LR and surfactant" group vs 282,5 ± 110,2 h in the "LR" group, p <0,01. There was no significant difference between two groups In mortality rate: 3 (15.8%) in the "LR and surfactant" group and 3 (21.4%) in the "LR" group. Conclusions. The combination of LR and surfactant administration decrease the time of respiratory support and ICU stay, reduce the risk of VAP.