Department of Orthopedic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
Department of Orthopaedics/Rheumatology/Hand Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Stem Cell Res Ther. 2024 Aug 13;15(1):259. doi: 10.1186/s13287-024-03842-w.
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.
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 × 10 cells, 2.1-2.7 × 10 cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip.
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.
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.
jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764 .
脊髓损伤（SCI）是一种毁灭性的损伤，由于其难治性，仍然是最大的医学和社会负担之一。根据干细胞生物学的最新进展，通过引入适当的干细胞，脊髓再生和功能恢复的可能性已经被提出。多谱系分化应激耐受（Muse）细胞是一种非肿瘤性内源性修复干细胞。先前已经显示出 Muse 细胞移植治疗 SCI 的阳性结果。作为在人类 SCI 中临床应用的第一步，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。
本研究的设计为前瞻性、多中心、非随机、非盲、单臂研究。临床试验注册号为 JRCT1080224764。纳入颈段 SCI 患者，神经损伤水平 C4 至 C7，改良 Frankel 分级 B1 和 B2，严重程度为 B1 和 B2。主要终点为安全性和可行性。我们的方案得到了 PMDA 的批准，该试验由日本东京生命科学研究所资助。本临床试验共招募 10 名参与者（8 名男性和 2 名女性），平均年龄 49.3±21.2 岁。所有 10 名参与者均接受单次剂量的同种异体 CL2020（共计 15×10 个细胞，体重 2.1-2.7×10 个细胞/kg），这是一种基于 Muse 细胞的产品，由人骨髓间充质干细胞制成，通过静脉滴注给药。
报告了两例严重不良事件，均与 Muse 细胞治疗无因果关系。与 CL2020 给药时相比，ISNCSCI 运动评分、日常生活活动和生活质量评分的变化显示出统计学意义上的显著改善。
在本试验中，未发现安全性问题， Muse 细胞产品移植具有良好的耐受性。未来的临床试验，采用适当的研究设计，纳入对照臂，将明确单次静脉注射同种异体 Muse 细胞治疗 SCI 的确切疗效。
jRCT，JRCT1080224764。注册于 2019 年 7 月 3 日，https://jrct.niph.go.jp/latest-detail/jRCT1080224764。
