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缺血性中风患者神经干细胞/祖细胞与间充质基质细胞共移植的两年随访研究

A two-year follow-up study of cotransplantation with neural stem/progenitor cells and mesenchymal stromal cells in ischemic stroke patients.

作者信息

Qiao Li-yan, Huang Fang-jie, Zhao Mangsuo, Xie Jing-hui, Shi Jie, Wang Jing, Lin Xian-zhong, Zuo Huancong, Wang Yun-liang, Geng Tong-chao

机构信息

Department of Neurology, Yuquan Hospital of Tsinghua University, Beijing, China.

出版信息

Cell Transplant. 2014;23 Suppl 1:S65-72. doi: 10.3727/096368914X684961. Epub 2014 Oct 20.

DOI:10.3727/096368914X684961
PMID:25333752
Abstract

Stem cell therapy is an emerging therapeutic modality in the treatment of stroke. We assessed the safety and feasibility of the cotransplantation of neural stem/progenitor cells (NSPCs) and mesenchymal stromal cells (MSCs) in patients with ischemic stroke. Eight patients were enrolled in this study. All patients had a hemisphere with infarct lesions located on one side of the territories of the cerebral middle or anterior arteries as revealed with cranial magnetic resonance imaging (MRI). The patients received one of the following two types of treatment: the first treatment involved four intravenous injections of MSCs at 0.5 × 10(6)/kg body weight; the second treatment involved one intravenous injection of MSCs at 0.5 × 10(6)/kg weight followed by three injections of MSCs at 5 × 10(6)/patient and NSPCs at 6 × 10(6)/patient through the cerebellomedullary cistern. The patients' clinical statuses were evaluated with the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel index (BI). Six patients were given four cell transplantations. The most common side effect of stem cell transplantation in these six cases was low fever that usually lasted 2-4 days after each therapy. One patient exhibited minor dizziness. All side effects appeared within the first 2-24 h of cell transplantation, and they resolved without special treatment. There was no evidence of neurological deterioration or neurological infection. Most importantly, no tumorigenesis was found at a 2-year follow-up. The neurological functions, disability levels, and daily living abilities of the patients in this study were improved. While these observations support the use of the combination transplantation of NSPCs and MSCs as a safe and feasible method of improving neurological function, further studies that include larger samples, longer follow-ups, and control groups are still needed. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.

摘要

干细胞疗法是治疗中风的一种新兴治疗方式。我们评估了神经干/祖细胞(NSPCs)和间充质基质细胞(MSCs)联合移植治疗缺血性中风患者的安全性和可行性。本研究纳入了8例患者。所有患者经头颅磁共振成像(MRI)显示,其一侧大脑半球存在位于大脑中动脉或前动脉供血区域的梗死灶。患者接受以下两种治疗方式之一:第一种治疗是静脉注射4次MSCs,剂量为0.5×10⁶/kg体重;第二种治疗是先静脉注射1次剂量为0.5×10⁶/kg体重的MSCs,随后通过小脑延髓池注射3次,每次剂量为5×10⁶个/患者的MSCs以及6×10⁶个/患者的NSPCs。采用美国国立卫生研究院卒中量表(NIHSS)、改良Rankin量表(mRS)和Barthel指数(BI)对患者的临床状况进行评估。6例患者接受了4次细胞移植。这6例患者中干细胞移植最常见的副作用是低热,通常在每次治疗后持续2 - 4天。1例患者出现轻微头晕。所有副作用均出现在细胞移植后的最初2 - 24小时内,未经特殊治疗自行缓解。没有神经功能恶化或神经感染的证据。最重要的是,在2年的随访中未发现肿瘤形成。本研究中患者的神经功能、残疾程度和日常生活能力均得到改善。虽然这些观察结果支持NSPCs和MSCs联合移植作为改善神经功能的一种安全可行的方法,但仍需要进一步开展包括更大样本量、更长随访时间和对照组的研究。本手稿作为国际神经修复学会(IANR)《细胞移植》特刊的一部分发表。

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