Giordano Rosaria, Canesi Margherita, Isalberti Maurizio, Marfia Giovanni, Campanella Rolando, Vincenti Daniele, Cereda Viviana, Ranghetti Alessandra, Palmisano Chiara, Isaias Ioannis Ugo, Benti Riccardo, Marotta Giorgio, Lazzari Lorenza, Montemurro Tiziana, Viganò Mariele, Budelli Silvia, Montelatici Elisa, Lavazza Cristiana, Rivera-Ordaz Araceli, Pezzoli Gianni
Laboratory of Regenerative Medicine - Cell Factory, Center of Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Parkinson Institute, ASST G. Pini-CTO, Milan, Italy.
Front Neurosci. 2021 Oct 12;15:723227. doi: 10.3389/fnins.2021.723227. eCollection 2021.
Mesenchymal stromal cells (MSCs) are multipotent cells with anti-inflammatory properties. Here we tested the safety of MSCs in patients with progressive supranuclear palsy (PSP; ClinicalTrials.gov: NCT01824121; Eudract No. 2011-004051-39). Seven patients were treated. To improve the safety, protocol adjustments were made during the performance of the study. The objectives of our work were: (1) to assess the safety of MSCs and (2) to identify critical issues in cell therapies for neurodegenerative diseases. Autologous MSCs from the bone marrow of PSP patients were administered through the internal carotid arteries. 1-year survival and number of severe adverse events were considered as safety endpoints. Clinical rating scales, neuropsychological assessments, gait and posture analysis, single-photon emission computed tomography, positron emission tomography, and brain magnetic resonance (BMR) were performed at different follow-up times. Peripheral blood levels of inflammatory cytokines were measured before and after cell infusion. Six of the seven treated patients were living 1 year after cell infusion. Asymptomatic spotty lesions were observed at BMR after 24 h in six of the seven treated patients. The last patient in the preliminary cohort (Case 5) exhibited transiently symptomatic BMR ischemic alterations. No severe adverse events were recorded in the last two treated patients. Interleukin-8 serum concentrations decreased in three patients (Case 2, 3, and 4). An adaptive study design, appropriate and up-to-date efficacy measures, adequate sample size estimation, and, possibly, the use of a cellular and/or allogeneic cell sources may help in performing phase II trials in the field.
间充质基质细胞（MSCs）是具有抗炎特性的多能细胞。在此，我们测试了MSCs对进行性核上性麻痹（PSP；ClinicalTrials.gov：NCT01824121；欧盟临床试验编号：2011 - 004051 - 39）患者的安全性。七名患者接受了治疗。为提高安全性，在研究实施过程中对方案进行了调整。我们工作的目标是：（1）评估MSCs的安全性；（2）确定神经退行性疾病细胞治疗中的关键问题。将来自PSP患者骨髓的自体MSCs通过颈内动脉给药。将1年生存率和严重不良事件的数量作为安全终点。在不同的随访时间进行临床评分量表、神经心理学评估、步态和姿势分析、单光子发射计算机断层扫描、正电子发射断层扫描以及脑磁共振成像（BMR）。在细胞输注前后测量外周血炎症细胞因子水平。七名接受治疗的患者中有六名在细胞输注后存活了1年。七名接受治疗的患者中有六名在24小时后的BMR检查中观察到无症状的斑点状病变。初步队列中的最后一名患者（病例5）出现了短暂有症状的BMR缺血性改变。最后两名接受治疗的患者未记录到严重不良事件。三名患者（病例2、3和4）的白细胞介素 - 8血清浓度下降。一种适应性研究设计、适当且最新的疗效测量方法、足够的样本量估计，以及可能使用细胞和/或同种异体细胞来源，可能有助于在该领域开展II期试验。
