Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial.
Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial.
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DOI：
10.1002/sctm.17-0219
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发表时间：
2018-12
影响因子：
6
通讯作者：
Park WS
中科院分区：
文献类型：
--
作者：
Ahn SY;Chang YS;Sung SI;Park WS
我们之前证明，移植间充质干细胞（MSC）可以改善新生大鼠因严重脑室内出血（IVH）引起的脑损伤的恢复。为了评估 MSC 在患有严重 IVH 的早产儿中的安全性和可行性，我们进行了 I 期剂量递增临床试验。前三名患者接受了低剂量的 MSC（5 × 106 个细胞/kg），接下来的六名患者接受了高剂量（1 × 107 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。对 9 名早产儿进行了脑室内移植，平均胎龄为 26.1 ± 0.7 周，出生后 11.6 ± 0.9 天出生体重为 808 ± 85 g。间充质干细胞治疗的耐受性良好，没有患者出现因间充质干细胞移植引起的严重不良反应或剂量限制性毒性。接受 MSC 的 IVH 患者没有死亡。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) 中显示出更高水平的白细胞介素 (IL)-6。最初获得的脑脊液中 IL-6 和肿瘤坏死因子-α 的水平与基线心室指数显着相关。将同种异体人 UCB 衍生的 MSC 脑室内移植到患有严重 IVH 的早产儿中是安全可行的，并且需要进行更大规模的受控 II 期研究。干细胞转化医学 2018；7:847–856
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 × 106 cells/kg), and the next six received a high dose (1 × 107 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
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