同种异体人脐带间充质干细胞来源的胞外体鞘内注射在完全亚急性脊髓损伤中的安全性和潜在作用：首例人体、单臂、开放标签、I 期临床试验。
Safety and potential effects of intrathecal injection of allogeneic human umbilical cord mesenchymal stem cell-derived exosomes in complete subacute spinal cord injury: a first-in-human, single-arm, open-label, phase I clinical trial.
机构信息
Medical Biotechnology Research Center, AJA University of Medical Sciences, PO box: 1411718541, Tehran, Iran.
Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, PO box: 1988873554, Tehran, Iran.
出版信息
Stem Cell Res Ther. 2024 Aug 26;15(1):264. doi: 10.1186/s13287-024-03868-0.
OBJECTIVE
Neurological and functional impairments are commonly observed in individuals with spinal cord injury (SCI) due to insufficient regeneration of damaged axons. Exosomes play a crucial role in the paracrine effects of mesenchymal stem cells (MSCs) and have emerged as a promising therapeutic approach for SCI. Thus, this study aimed to evaluate the safety and potential effects of intrathecal administration of allogeneic exosomes derived from human umbilical cord MSCs (HUC-MSCs) in patients with complete subacute SCI.
METHODS
This study was a single-arm, open-label, phase I clinical trial with a 12-month follow-up period. HUC-MSCs were extracted from human umbilical cord tissue, and exosomes were isolated via ultracentrifugation. After intrathecal injection, each participant a underwent complete evaluation, including neurological assessment using the American Spinal Injury Association (ASIA) scale, functional assessment using the Spinal Cord Independence Measure (SCIM-III), neurogenic bowel dysfunction (NBD) assessment using the NBD score, modified Ashworth scale (MAS), and lower urinary tract function questionnaire.
RESULTS
Nine patients with complete subacute SCI were recruited. The intrathecal injection of allogeneic HUC-MSCs-exosomes was safe and well tolerated. No early or late adverse event (AE) attributable to the study intervention was observed. Significant improvements in ASIA pinprick (P-value = 0.039) and light touch (P-value = 0.038) scores, SCIM III total score (P-value = 0.027), and NBD score (P-value = 0.042) were also observed at 12-month after the injection compared with baseline.
CONCLUSIONS
This study demonstrated that intrathecal administration of allogeneic HUC-MSCs-exosomes is safe in patients with subacute SCI. Moreover, it seems that this therapy might be associated with potential clinical and functional improvements in these patients. In this regard, future larger phase II/III clinical trials with adequate power are highly required.
TRIAL REGISTRATION
Iranian Registry of Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765 .
目的
由于受损轴突的再生不足，脊髓损伤（SCI）患者常出现神经和功能损伤。外泌体在间充质干细胞（MSCs）的旁分泌作用中发挥着重要作用，并且已成为 SCI 的一种有前途的治疗方法。因此，本研究旨在评估鞘内给予人脐带 MSC（HUC-MSC）来源的同种异体外泌体在完全亚急性 SCI 患者中的安全性和潜在疗效。
方法
这是一项单臂、开放标签、I 期临床试验，随访 12 个月。从人脐带组织中提取 HUC-MSC，通过超速离心分离外泌体。鞘内注射后，每位参与者均接受全面评估，包括使用美国脊髓损伤协会（ASIA）量表进行神经评估、使用脊髓独立性量表（SCIM-III）进行功能评估、使用 NBD 评分、改良 Ashworth 量表（MAS）和下尿路功能问卷进行神经源性肠道功能障碍（NBD）评估。
结果
共纳入 9 例完全亚急性 SCI 患者。同种异体 HUC-MSC-外泌体鞘内注射安全且耐受良好。未观察到与研究干预相关的早期或晚期不良事件（AE）。与基线相比，注射后 12 个月时 ASIA 针刺痛觉（P 值=0.039）和轻触觉（P 值=0.038）评分、SCIM III 总分（P 值=0.027）和 NBD 评分（P 值=0.042）均显著改善。
结论
本研究表明，鞘内给予亚急性 SCI 患者同种异体 HUC-MSC-外泌体是安全的。此外，这种治疗方法似乎与这些患者的潜在临床和功能改善有关。在这方面，需要进行具有足够效力的更大规模的 II/III 期临床试验。
试验注册
伊朗临床试验注册中心，IRCT20200502047277N1。于 2020 年 10 月 2 日注册，https://en.irct.ir/trial/48765。
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