Department of Pediatrics, Samsung Medical Center and Sungkyunkwan University School of Medicine, Seoul, South Korea.
Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, South Korea.
Stem Cells Transl Med. 2021 Aug;10(8):1129-1137. doi: 10.1002/sctm.20-0330. Epub 2021 Apr 20.
We previously demonstrated the safety and feasibility of mesenchymal stem cell (MSC) transplantation for bronchopulmonary dysplasia (BPD) in preterm infants in a phase I clinical trial. We thus investigated the therapeutic efficacy of MSCs for BPD in premature infants. A phase II double-blind, randomized, placebo-controlled clinical trial was conducted on preterm infants at 23 to 28 gestational weeks (GW) receiving mechanical ventilator support with respiratory deterioration between postnatal days 5 and 14. Infants were stratified by 23 to 24 GW and 25 to 28 GW and randomly allocated (1:1) to receive stem cells (1 × 10 cells/kg, n = 33) or placebo (n = 33). Although the inflammatory cytokines in the tracheal aspirate fluid were significantly reduced with MSCs, the primary outcome of death or severe/moderate BPD in the control group (18/33, 55%) was not significantly improved with MSC transplantation (17/33, 52%). In the subgroup analysis, the secondary outcome of severe BPD was significantly improved from 53% (8/15) to 19% (3/16) with MSC transplantation in the 23 to 24 GW group but not in the 25 to 28 GW subgroup. In summary, although MSC transplantation might be safe and feasible, this small study was underpowered to detect its therapeutic efficacy in preterm infants at 23 to 28 GW. Accordingly, we are now conducting an additional larger and controlled phase II clinical trial focusing on infants at 23 to 24 GW (NCT03392467). ClinicalTrials.gov identifier: NCT01828957.
我们之前在一项 I 期临床试验中证明了间充质干细胞（MSC）移植治疗早产儿支气管肺发育不良（BPD）的安全性和可行性。因此，我们研究了 MSCs 治疗早产儿 BPD 的疗效。一项 23 至 28 孕周（GW）的接受机械通气支持且在出生后 5 至 14 天期间出现呼吸恶化的早产儿的 II 期双盲、随机、安慰剂对照临床试验进行。根据 23 至 24 GW 和 25 至 28 GW 对婴儿进行分层，并按 1:1 比例随机分配（1×10 细胞/kg，n=33）接受干细胞（n=33）或安慰剂。尽管 MSC 治疗可显著降低气管抽吸液中的炎症细胞因子，但对照组（18/33，55%）的主要结局（死亡或严重/中度 BPD）并未因 MSC 移植而显著改善（17/33，52%）。在亚组分析中，在 23 至 24 GW 组中，MSC 移植可将严重 BPD 的次要结局从 53%（8/15）显著改善至 19%（3/16），但在 25 至 28 GW 亚组中则不然。总之，尽管 MSC 移植可能是安全可行的，但这项小型研究没有足够的能力来检测其在 23 至 28 GW 早产儿中的治疗效果。因此，我们目前正在进行一项额外的、更大规模的、针对 23 至 24 GW 婴儿的 II 期对照临床试验（NCT03392467）。临床试验注册：NCT01828957。
