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创伤性脑损伤中的神经保护:间充质基质细胞可能克服以往临床试验的一些局限性。

Neuroprotection in Traumatic Brain Injury: Mesenchymal Stromal Cells can Potentially Overcome Some Limitations of Previous Clinical Trials.

作者信息

Carbonara Marco, Fossi Francesca, Zoerle Tommaso, Ortolano Fabrizio, Moro Federico, Pischiutta Francesca, Zanier Elisa R, Stocchetti Nino

机构信息

Neuroscience Intensive Care Unit, Department of Anaesthesia and Critical Care, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.

Laboratory of Acute Brain Injury and Therapeutic Strategies, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

出版信息

Front Neurol. 2018 Oct 24;9:885. doi: 10.3389/fneur.2018.00885. eCollection 2018.

Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. In the last 30 years several neuroprotective agents, attenuating the downstream molecular and cellular damaging events triggered by TBI, have been extensively studied. Even though many drugs have shown promising results in the pre-clinical stage, all have failed in large clinical trials. Mesenchymal stromal cells (MSCs) may offer a promising new therapeutic intervention, with preclinical data showing protection of the injured brain. We selected three of the critical aspects identified as possible causes of clinical failure: the window of opportunity for drug administration, the double-edged contribution of mechanisms to damage and recovery, and the oft-neglected role of reparative mechanisms. For each aspect, we briefly summarized the limitations of previous trials and the potential advantages of a newer approach using MSCs.

摘要

创伤性脑损伤(TBI)是全球范围内死亡和残疾的主要原因。在过去30年中,几种神经保护剂已被广泛研究,这些药物可减轻TBI引发的下游分子和细胞损伤事件。尽管许多药物在临床前阶段已显示出有希望的结果,但在大型临床试验中均告失败。间充质基质细胞(MSCs)可能提供一种有前景的新治疗干预措施,临床前数据表明其对受伤大脑具有保护作用。我们选择了被确定为临床失败可能原因的三个关键方面:药物给药的时机窗、机制对损伤和恢复的双重作用以及常常被忽视的修复机制的作用。对于每个方面,我们简要总结了先前试验的局限性以及使用MSCs的新方法的潜在优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24b7/6208094/c263906e29fa/fneur-09-00885-g0001.jpg

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