de Celis-Ruiz Elena, Fuentes Blanca, Alonso de Leciñana María, Gutiérrez-Fernández María, Borobia Alberto M, Gutiérrez-Zúñiga Raquel, Ruiz-Ares Gerardo, Otero-Ortega Laura, Laso-García Fernando, Gómez-de Frutos Mari Carmen, Díez-Tejedor Exuperio
Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autónoma de Madrid), Madrid, Spain.
Department of Clinical Pharmacology, Hospital la Paz Institute for Health Research-IdiPAZ (La Paz University Hospital, Universidad Autónoma de Madrid), Madrid, Spain.
Cell Transplant. 2022 Jan-Dec;31:9636897221083863. doi: 10.1177/09636897221083863.
Acute ischemic stroke is currently a major cause of disability despite improvement in recanalization therapies. Stem cells represent a promising innovative strategy focused on reduction of neurologic sequelae by enhancement of brain plasticity. We performed a phase IIa, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Patients aged ≥60 years with moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] 8-20) were randomized (1:1) to receive intravenous adipose tissue-derived mesenchymal stem cells (AD-MSCs) or placebo within the first 2 weeks of stroke onset. The primary outcome was safety, evaluating adverse events (AEs), neurologic and systemic complications, and tumor development. The secondary outcome evaluated treatment efficacy by measuring modified Rankin Scale (mRS), NIHSS, infarct size, and blood biomarkers. We report the final trial results after 24 months of follow-up. Recruitment began in December 2014 and stopped in December 2017 after 19 of 20 planned patients were included. Six patients did not receive study treatment: two due to technical issues and four for acquiring exclusion criteria after randomization. The final study sample was composed of 13 patients (4 receiving AD-MSCs and 9 placebo). One patient in the placebo group died within the first week after study treatment delivery due to sepsis. Two non-treatment-related serious AEs occurred in the AD-MSC group and nine in the placebo group. The total number of AEs and systemic or neurologic complications was similar between the study groups. No injection-related AEs were registered, nor tumor development. At 24 months of follow-up, patients in the AD-MSC group showed a nonsignificantly lower median NIHSS score (interquartile range, 3 [3-5.5] vs 7 [0-8]). Neither treatment group had differences in mRS scores throughout follow-up visits up to month 24. Therefore, intravenous treatment with AD-MSCs within the first 2 weeks from ischemic stroke was safe at 24 months of follow-up.
尽管再通治疗有所改善，但急性缺血性中风目前仍是导致残疾的主要原因。干细胞是一种很有前景的创新策略，其重点是通过增强脑可塑性来减少神经后遗症。我们进行了一项IIa期、随机、双盲、安慰剂对照、单中心的试点临床试验。年龄≥60岁、患有中度至重度中风（美国国立卫生研究院卒中量表[NIHSS]评分8 - 20）的患者在中风发作后的前2周内被随机分组（1:1），接受静脉注射脂肪组织来源的间充质干细胞（AD - MSC）或安慰剂。主要结局是安全性，评估不良事件（AE）、神经和全身并发症以及肿瘤发生情况。次要结局通过测量改良Rankin量表（mRS）、NIHSS、梗死灶大小和血液生物标志物来评估治疗效果。我们报告了随访24个月后的最终试验结果。招募工作于2014年12月开始，在纳入计划的20名患者中的19名后，于2017年12月停止。6名患者未接受研究治疗：2名是由于技术问题，4名是在随机分组后获得排除标准。最终研究样本由13名患者组成（4名接受AD - MSC治疗，9名接受安慰剂治疗）。安慰剂组的1名患者在研究治疗给药后的第一周内死于败血症。AD - MSC组发生了2例与治疗无关的严重AE，安慰剂组发生了9例。研究组之间AE以及全身或神经并发症的总数相似。未记录到与注射相关的AE，也未发生肿瘤。在随访24个月时，AD - MSC组患者的NIHSS中位数评分略低，但无统计学意义（四分位间距，3[3 - 5.5]对7[0 - 8]）。在直至第24个月的整个随访期间，两个治疗组的mRS评分均无差异。因此，在缺血性中风后的前2周内静脉注射AD - MSC在随访24个月时是安全的。
