Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea.
Stem Cells Transl Med. 2018 Dec;7(12):847-856. doi: 10.1002/sctm.17-0219. Epub 2018 Aug 21.
We previously demonstrated that transplanting mesenchymal stem cells (MSCs) improved recovery from brain injury induced by severe intraventricular hemorrhage (IVH) in newborn rats. To assess the safety and feasibility of MSCs in preterm infants with severe IVH, we performed a phase I dose-escalation clinical trial. The first three patients received a low dose of MSCs (5 × 10 cells/kg), and the next six received a high dose (1 × 10 cells/kg). We assessed adverse outcomes, including mortality and the progress of posthemorrhagic hydrocephalus. Intraventricular transplantation of MSCs was performed in nine premature infants with mean gestational age of 26.1 ± 0.7 weeks and birth weight of 808 ± 85 g at 11.6 ± 0.9 postnatal days. Treatment with MSCs was well tolerated, and no patients showed serious adverse effects or dose-limiting toxicities attributable to MSC transplantation. There was no mortality in IVH patients receiving MSCs. Infants who underwent shunt surgery showed a higher level of interleukin (IL)-6 in cerebrospinal fluid (CSF) obtained before MSC transplantation in comparison with infants who did not receive a shunt. Levels of IL-6 and tumor necrosis factor-α in initially obtained CSF correlated significantly with baseline ventricular index. Intraventricular transplantation of allogeneic human UCB-derived MSCs into preterm infants with severe IVH is safe and feasible, and warrants a larger, and controlled, phase II study. Stem Cells Translational Medicine 2018;7:847-856.
我们之前的研究表明，移植间充质干细胞（MSCs）可改善新生大鼠严重脑室出血（IVH）引起的脑损伤的恢复。为了评估 MSCs 在患有严重 IVH 的早产儿中的安全性和可行性，我们进行了一项 I 期剂量递增临床试验。前 3 名患者接受了低剂量 MSCs（5×10 个细胞/kg），接下来的 6 名患者接受了高剂量（1×10 个细胞/kg）。我们评估了不良结局，包括死亡率和出血后脑积水的进展。9 名早产儿在出生后 11.6±0.9 天，平均胎龄为 26.1±0.7 周，出生体重为 808±85g 时，进行了脑室内 MSCs 移植。MSCs 治疗耐受良好，没有患者表现出与 MSC 移植相关的严重不良事件或剂量限制毒性。接受 MSCs 的 IVH 患者无死亡。与未接受分流手术的婴儿相比，接受分流手术的婴儿在 MSC 移植前获得的脑脊液（CSF）中白细胞介素（IL）-6 水平更高。最初获得的 CSF 中 IL-6 和肿瘤坏死因子-α的水平与基线脑室指数显著相关。将同种异体人 UCB 来源的 MSCs 脑室内移植到患有严重 IVH 的早产儿中是安全可行的，需要进行更大规模的、对照的 II 期研究。《Stem Cells Translational Medicine》2018 年；7:847-856.
