Pan Kuang, Deng Lingna, Chen Peiying, Peng Qingxia, Pan Jingrui, Wu Yanfeng, Wang Yidong
Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Scientific Research Centre and Department of Orthopaedics, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
Stem Cells Int. 2019 Jul 25;2019:8421281. doi: 10.1155/2019/8421281. eCollection 2019.
Mesenchymal stromal cells (MSCs) have become the most commonly used adult stem cells in regenerative medicine. Preclinical studies have shown that MSCs-based therapy is a potential new treatment approach for neurological diseases. Intrathecal injection has unique feature which allows stem cells to directly migrate to the lesion site in patients with central nervous system (CNS) diseases. In this study, we evaluate the safety and feasibility of intrathecal allogeneic bone marrow-derived MSCs (BM-MSCs) in patients with neurological diseases. This open-label clinical study included 37 patients (14 diseases). Eligible patients underwent a baseline assessment and were intrathecally injected with allogeneic BM-MSCs (1 × 10 cells/kg, 4 consecutive treatments at 1-week intervals). After four infusions, the patients were followed up for at least 6 months. Adverse events, cerebrospinal fluid (CSF) test results, clinical symptoms, physical examination, and haematological and imaging examinations were used to assess the safety and feasibility of the treatment. Also, we performed a systematic review of the safety of all types of intrathecal stem cells and compared our result to previous studies. In our study, the highest adverse event was a slight ache at the injection site (4.11%), followed by fever (3.42%) and mild headache (2.05%). No severe adverse events were reported. After the intrathecal injections, the white blood cell (WBC) counts in the CSF increased in 30 patients and the protein concentration in the CSF exceeded the normal range in 26 patients, while other CSF indicators remained normal. Moreover, these patients had no suspected manifestations of CNS infection. Haematological and imaging examinations showed no abnormal changes after BM-MSCs infusion. Compared with previous studies, the incidence of adverse events was nearly consistent or even lower for headache, fever, nausea, and neck pain. In conclusion, repeated intrathecal allogeneic BM-MSCs are safe, feasible, and promising for the treatment of patients with neurological diseases.
间充质基质细胞（MSCs）已成为再生医学中最常用的成体干细胞。临床前研究表明，基于MSCs的治疗是一种治疗神经疾病的潜在新方法。鞘内注射具有独特的特点，可使干细胞直接迁移至中枢神经系统（CNS）疾病患者的病灶部位。在本研究中，我们评估了鞘内注射同种异体骨髓来源的MSCs（BM-MSCs）治疗神经疾病患者的安全性和可行性。这项开放标签的临床研究纳入了37例患者（涉及14种疾病）。符合条件的患者接受了基线评估，并接受了鞘内注射同种异体BM-MSCs（1×10⁶细胞/千克，连续4次治疗，间隔1周）。4次输注后，对患者进行了至少6个月的随访。通过不良事件、脑脊液（CSF）检测结果、临床症状、体格检查以及血液学和影像学检查来评估治疗的安全性和可行性。此外，我们对所有类型鞘内干细胞的安全性进行了系统评价，并将我们的结果与先前的研究进行了比较。在我们的研究中，最高的不良事件是注射部位轻微疼痛（4.11%），其次是发热（3.42%）和轻度头痛（2.05%）。未报告严重不良事件。鞘内注射后，30例患者脑脊液中的白细胞（WBC）计数增加，26例患者脑脊液中的蛋白质浓度超过正常范围，而其他脑脊液指标保持正常。此外，这些患者没有中枢神经系统感染的可疑表现。血液学和影像学检查显示BM-MSCs输注后无异常变化。与先前的研究相比，头痛、发热、恶心和颈部疼痛的不良事件发生率几乎一致甚至更低。总之，重复鞘内注射同种异体BM-MSCs治疗神经疾病患者是安全、可行且有前景的。
