PDF(Pubmed)
Abstract：
BACKGROUND: Spinal cord injury (SCI) is a devastating injury and remains one of the largest medical and social burdens because of its intractable nature. According to the recent advances in stem cell biology, the possibility of spinal cord regeneration and functional restoration has been suggested by introducing appropriate stem cells. Multilineage-differentiating stress enduring (Muse) cells are a type of nontumorigenic endogenous reparative stem cell. The positive results of Muse cell transplantation for SCI was shown previously. As a first step for clinical application in human SCI, we conducted a clinical trial aiming to confirm the safety and feasibility of intravenously injected donor-Muse cells.
METHODS: The study design of the current trial was a prospective, multicenter, nonrandomized, nonblinded, single-arm study. The clinical trial registration number was JRCT1080224764. Patients with a cervical SCI with a neurological level of injury C4 to C7 with the severity of modified Frankel classification B1 and B2 were included. A primary endpoint was set for safety and feasibility. Our protocol was approved by the PMDA, and the trial was funded by the Life Science Institute, Tokyo, Japan. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. All 10 participants received a single dose of allogenic CL2020 (a total of 15 × 106 cells, 2.1-2.7 × 105 cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip.
RESULTS: There were two reported severe adverse events, both of which were determined to have no causal relationship with Muse cell treatment. The change in the ISNCSCI motor score, the activity of daily living and quality of life scores showed statistically significant improvements compared to those data at the time of CL2020 administration.
CONCLUSIONS: In the present trial, no safety concerns were identified, and Muse cell product transplantation demonstrated good tolerability. Future clinical trials with appropriate study designs incorporating a control arm will clarify the definitive efficacy of single-dose allogenic Muse cell treatment with intravenous administration to treat SCI.
BACKGROUND: jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764 .
METHODS: The study design of the current trial was a prospective, multicenter, nonrandomized, nonblinded, single-arm study. The clinical trial registration number was JRCT1080224764. Patients with a cervical SCI with a neurological level of injury C4 to C7 with the severity of modified Frankel classification B1 and B2 were included. A primary endpoint was set for safety and feasibility. Our protocol was approved by the PMDA, and the trial was funded by the Life Science Institute, Tokyo, Japan. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. All 10 participants received a single dose of allogenic CL2020 (a total of 15 × 106 cells, 2.1-2.7 × 105 cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip.
RESULTS: There were two reported severe adverse events, both of which were determined to have no causal relationship with Muse cell treatment. The change in the ISNCSCI motor score, the activity of daily living and quality of life scores showed statistically significant improvements compared to those data at the time of CL2020 administration.
CONCLUSIONS: In the present trial, no safety concerns were identified, and Muse cell product transplantation demonstrated good tolerability. Future clinical trials with appropriate study designs incorporating a control arm will clarify the definitive efficacy of single-dose allogenic Muse cell treatment with intravenous administration to treat SCI.
BACKGROUND: jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764 .
摘要：
背景：脊髓损伤（SCI）是一种毁灭性的损伤，由于其棘手的性质，仍然是最大的医疗和社会负担之一。根据干细胞生物学的最新进展，脊髓再生和功能恢复的可能性已被认为通过引入适当的干细胞。多谱系分化应激持久（Muse）细胞是一种非致瘤内源性修复干细胞。先前显示了用于SCI的Muse细胞移植的阳性结果。作为人类SCI临床应用的第一步，我们进行了一项临床试验，旨在确认静脉注射供体Muse细胞的安全性和可行性。
方法：当前试验的研究设计是前瞻性的，多中心，非随机化，非盲化,单臂研究。临床试验登记号为JRCT1080224764。包括颈性SCI患者，其神经系统损伤程度为C4至C7，严重程度为改良的Frankel分类B1和B2。主要终点设定为安全性和可行性。我们的方案得到了PMDA的批准,这项试验由生命科学研究所资助，东京,日本。本临床试验招募了10名参与者(8名男性和2名女性),平均年龄为49.3±21.2岁。所有10名参与者均接受了单剂量的同种异体CL2020（总共15×106个细胞，2.1-2.7×105个细胞/kg体重），它是由人类间充质干细胞生产的Muse细胞产品，通过静脉滴注。
结果：报告了两次严重不良事件，两者都被确定与Muse细胞治疗没有因果关系。ISNCSCI运动评分的变化，与CL2020给药时的数据相比,日常生活活动能力和生活质量评分显示出统计学上显著的改善.
结论：在本试验中，没有发现安全问题，Muse细胞产品移植表现出良好的耐受性。结合对照臂的适当研究设计的未来临床试验将阐明静脉内给药单剂量同种异体Muse细胞治疗SCI的最终疗效。
背景：jRCT，JRCT1080224764。2019年7月3日注册，https://jrct。尼夫.走吧。jp/最新细节/jRCT1080224764。
方法：当前试验的研究设计是前瞻性的，多中心，非随机化，非盲化,单臂研究。临床试验登记号为JRCT1080224764。包括颈性SCI患者，其神经系统损伤程度为C4至C7，严重程度为改良的Frankel分类B1和B2。主要终点设定为安全性和可行性。我们的方案得到了PMDA的批准,这项试验由生命科学研究所资助，东京,日本。本临床试验招募了10名参与者(8名男性和2名女性),平均年龄为49.3±21.2岁。所有10名参与者均接受了单剂量的同种异体CL2020（总共15×106个细胞，2.1-2.7×105个细胞/kg体重），它是由人类间充质干细胞生产的Muse细胞产品，通过静脉滴注。
结果：报告了两次严重不良事件，两者都被确定与Muse细胞治疗没有因果关系。ISNCSCI运动评分的变化，与CL2020给药时的数据相比,日常生活活动能力和生活质量评分显示出统计学上显著的改善.
结论：在本试验中，没有发现安全问题，Muse细胞产品移植表现出良好的耐受性。结合对照臂的适当研究设计的未来临床试验将阐明静脉内给药单剂量同种异体Muse细胞治疗SCI的最终疗效。
背景：jRCT，JRCT1080224764。2019年7月3日注册，https://jrct。尼夫.走吧。jp/最新细节/jRCT1080224764。
