基于 Muse 细胞的产品在新生儿缺氧缺血性脑病治疗性低温中的安全性和耐受性(SHIELD 试验)。

IF 5.4 2区 医学 Q1 CELL & TISSUE ENGINEERING
Yoshiaki Sato, Shinobu Shimizu, Kazuto Ueda, Toshihiko Suzuki, Sakiko Suzuki, Ryosuke Miura, Masahiko Ando, Kennosuke Tsuda, Osuke Iwata, Yukako Muramatsu, Hiroyuki Kidokoro, Akihiro Hirakawa, Masahiro Hayakawa
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引用次数: 0

摘要

缺氧缺血性脑病(HIE)与高死亡率和神经系统后遗症有关,除治疗性低温外,缺乏成熟的治疗方法。临床级多线粒体分化应激耐受(Muse)细胞(CL2020)在非临床HIE大鼠模型中表现出安全性和有效性,因此研究人员发起了一项临床试验,评估CL2020在新生儿HIE中的安全性和耐受性,这是一项单中心开放标签剂量递增研究,9名患有中重度HIE的新生儿接受了治疗性低温。每位患者都在出生后 5 到 14 天之间接受了一次 CL2020 细胞静脉注射。低剂量组(3 名患者)和高剂量组(6 名患者)分别接受了 1.5 × 106 和 1.5 × 107 个细胞/剂量。CL2020用药后12周内发生任何不良事件是本试验的主要终点。用药期间或用药后,心率、血压和血氧饱和度等生理指标均未出现明显变化。唯一可能与细胞给药有关的不良反应是一名新生儿出现轻微的γ-谷氨酰转移酶水平升高,无需任何治疗即可自行缓解。所有参加试验的患者都存活了下来,67%的患者在 2001 年京都心理发展量表的所有 3 个领域中都观察到了正常的发展商数(≥ 85)。试验证明,CL2020 对患有 HIE 的新生儿是安全和可耐受的。考虑到患者人数较少,有必要进行随机对照确证研究,以验证这些初步发现并评估该疗法的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Safety and tolerability of a Muse cell-based product in neonatal hypoxic-ischemic encephalopathy with therapeutic hypothermia (SHIELD trial).

Hypoxic-ischemic encephalopathy (HIE), associated with high mortality and neurological sequelae, lacks established treatment except therapeutic hypothermia. Clinical-grade multilineage-differentiating stress-enduring (Muse) cells (CL2020) demonstrated safety and efficacy in nonclinical HIE rat models, thereby leading to an investigator-initiated clinical trial to evaluate CL2020 safety and tolerability in neonatal HIE as a single-center open-label dose-escalation study with 9 neonates with moderate-to-severe HIE who received therapeutic hypothermia. Each patient received a single intravenous injection of CL2020 cells between 5 and 14 days of age. The low-dose (3 patients) and high-dose (6 patients) groups received 1.5 × 106 and 1.5 × 107 cells/dose, respectively. The occurrence of any adverse event within 12 weeks following CL2020 administration was the primary endpoint of this trial. No significant changes in physiological signs including heart rate, blood pressure, and oxygen saturation were observed during or after administration. The only adverse event that may be related to cell administration was a mild γ-glutamyltransferase level elevation in one neonate, which spontaneously resolved without any treatment. All patients enrolled in the trial survived, and normal developmental quotients (≥ 85) in all 3 domains of the Kyoto Scale of Psychological Development 2001 were observed in 67% of the patients in this trial. CL2020 administration was demonstrated to be safe and tolerable for neonates with HIE. Considering the small number of patients, a randomized controlled confirmatory study is warranted to verify these preliminary findings and evaluate the efficacy of this therapy.

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来源期刊
Stem Cells Translational Medicine
Stem Cells Translational Medicine CELL & TISSUE ENGINEERING-
CiteScore
12.90
自引率
3.30%
发文量
140
审稿时长
6-12 weeks
期刊介绍: STEM CELLS Translational Medicine is a monthly, peer-reviewed, largely online, open access journal. STEM CELLS Translational Medicine works to advance the utilization of cells for clinical therapy. By bridging stem cell molecular and biological research and helping speed translations of emerging lab discoveries into clinical trials, STEM CELLS Translational Medicine will help move applications of these critical investigations closer to accepted best patient practices and ultimately improve outcomes. The journal encourages original research articles and concise reviews describing laboratory investigations of stem cells, including their characterization and manipulation, and the translation of their clinical aspects of from the bench to patient care. STEM CELLS Translational Medicine covers all aspects of translational cell studies, including bench research, first-in-human case studies, and relevant clinical trials.
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