Serious adverse events of cell therapy for respiratory diseases: a systematic review and meta-analysis.

BACKGROUND: Cell therapy holds the most promising for acute and chronic deleterious respiratory diseases. However, the safety and tolerance for lung disorders are controversy.

METHODS: We undertook a systematic review and meta-analyses of all 23 clinical studies of cell therapy. The outcomes were odds ratio (OR), risk difference (RD), Peto OR, relative risk, and mean difference of serious adverse events.

RESULTS: 342 systemic infusions and 57 bronchial instillations (204 recipients) of cells were analyzed for acute respiratory distress syndrome (ARDS), bronchopulmonary dysplasia, pulmonary arterial hypertension, silicosis, sarcoidosis, extensively drug-resistant tuberculosis, chronic obstructive pulmonary diseases (COPD), and idiopathic pulmonary fibrosis. The frequency of death in adults from any causes was 71 and 177 per 1,000 for cell therapy and controls, respectively, with an OR of 0.31 (95% CI: 0.03, 3.76) and RD of -0.22 (95% CI: -0.53, 0.09). No significant difference was found for ARDS and COPD. The frequency of deaths and non-fatal serious adverse events of 17 open studies were similar to those of randomized controlled trials. Moreover, serious adverse events of allogenic cells were greater than autologous preparations, as shown by frequency, OR and RD.

CONCLUSIONS: We conclude that either infusion or instillation of mesenchymal stem stromal or progenitor cells are well tolerated without serious adverse events causally related to cell treatment. Cell therapy has not been associated with significant changes in spirometry, immune function, cardiovascular activity, and the quality of life.