Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Crit Care Med. 2020 May;48(5):e391-e399. doi: 10.1097/CCM.0000000000004285.
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 × 10 cells/kg), the next three patients with intermediate dose (5.0 × 10 cells/kg), and the final three patients with high dose (1.0 × 10 cells/kg) between December 2017 and August 2019.
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 (CD14CD33/CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14CD33+) 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/Cytotoxity-T-cell/Regulatory-T-cell) 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.
研究单次剂量人脐带间充质干细胞治疗中重度急性呼吸窘迫综合征患者的安全性、可行性和可能的不良反应。
前瞻性 I 期临床试验。
中国台湾高雄市医疗中心。
中重度急性呼吸窘迫综合征，氧合指数（PaO2/FIO2）＜200。
根据台湾食品药品监督管理局的要求进行剂量分级：2017 年 12 月至 2019 年 8 月，前 3 例患者接受低剂量（1.0×10^6 细胞/kg），接下来 3 例接受中剂量（5.0×10^6 细胞/kg），最后 3 例接受高剂量（1.0×10^6 细胞/kg）。
连续纳入 9 例患者。住院病死率为 33.3%（3/9），其中 2 例患者出现复发性感染性休克，1 例患者出现呼吸机相关性严重纵隔气肿和皮下气肿。未发现任何与细胞输注相关或与治疗相关的严重不良事件。连续流式细胞术分析循环炎症生物标志物（CD14CD33/CD11b+CD16+/CD16+MPO+/CD11b+MPO+/CD14CD33+）和间充质干细胞标志物（CD26+CD45-/CD29+CD45-/CD34+CD45-/CD44+CD45-/CD73+CD45-/CD90+CD45-/CD105+CD45-/CD26+CD45-）明显逐渐降低（p 趋势＜0.001），而免疫细胞标志物（辅助性 T 细胞/细胞毒性 T 细胞/调节性 T 细胞）明显增加（p 趋势＜0.001）。
这项 I 期临床试验的结果表明，单次静脉输注人脐带间充质干细胞治疗 9 例急性呼吸窘迫综合征患者是安全的，且结果良好。
