Human Umbilical Cord-Derived Mesenchymal Stem Cells for Acute Respiratory Distress Syndrome

Objectives: To investigate the safety, feasibility, and possible adverse events of single-dose human umbilical cord-derived mesenchymal stem cells in patients with moderate-to-severe acute respiratory distress syndrome. Design: Prospective phase I clinical trial. Setting: Medical center in Kaohsiung, Taiwan. Patients: Moderate-to-severe acute respiratory distress syndrome with a Pa o 2 /F io 2 ratio less than 200. Interventions: Scaling for doses was required by Taiwan Food and Drug Administration as follows: the first three patients received low-dose human umbilical cord-derived mesenchymal stem cells (1.0 × 10 6 cells/kg), the next three patients with intermediate dose (5.0 × 10 6 cells/kg), and the final three patients with high dose (1.0 × 10 7 cells/kg) between December 2017 and August 2019. Measurements and Main Results: Nine consecutive patients were enrolled into the study. In-hospital mortality was 33.3% (3/9), including two with recurrent septic shock and one with ventilator-induced severe pneumomediastinum and subcutaneous emphysema. No serious prespecified cell infusion-associated or treatment-related adverse events was identified in any patient. Serial flow-cytometric analyses of circulating inflammatory biomarkers (CD14 + CD33 + /CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14 dim CD33+) and mesenchymal stem cell markers (CD26+CD45–/CD29+CD45–/CD34+CD45–/CD44+CD45–/CD73+CD45–/CD90+CD45–/CD105+CD45–/CD26+CD45–) were notably progressively reduced ( p for trend < 0.001), whereas the immune cell markers (Helper-T-cell CD3+CD4+ /Cytotoxity-T-cell CD3+CD8+ /Regulatory-T-cell CD4+CD25+FOXp3+ ) were notably increased ( p for trend < 0.001) after cell infusion. Conclusions: The result of this phase I clinical trial showed that a single-dose IV infusion of human umbilical cord-derived mesenchymal stem cells was safe with favorable outcome in nine acute respiratory distress syndrome patients.