Abstract
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 Pao2/Fio2ratio 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 × 106cells/kg), the next three patients with intermediate dose (5.0 × 106cells/kg), and the final three patients with high dose (1.0 × 107cells/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. 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.
Original language | English |
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Pages (from-to) | E391-E399 |
Journal | Critical Care Medicine |
Volume | 48 |
Issue number | 5 |
DOIs | |
State | Published - 01 05 2020 |
Bibliographical note
Publisher Copyright:© 2020 Lippincott Williams and Wilkins. All rights reserved.
Keywords
- acute respiratory distress syndrome
- allogenic mesenchymal stem cells
- in-hospital mortality
- inflammation
- sepsis