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.
Prospective phase I clinical trial.
Medical center in Kaohsiung, Taiwan.
Moderate-to-severe acute respiratory distress syndrome with a Pao2/Fio2 ratio less than 200.
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 × 106 cells/kg), the next three patients with intermediate dose (5.0 × 106 cells/kg), and the final three patients with high dose (1.0 × 107 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+/CD14dimCD33+) 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-cellCD3+CD4+/Cytotoxity-T-cellCD3+CD8+/Regulatory-T-cellCD4+CD25+FOXp3+) were notably increased (p for trend < 0.001) after cell infusion.
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.