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中枢神经系统修复的多靶点方法:嗅黏膜来源的细胞和硫酸乙酰肝素。

Multi-target approaches to CNS repair: olfactory mucosa-derived cells and heparan sulfates.

机构信息

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

出版信息

Nat Rev Neurol. 2020 Apr;16(4):229-240. doi: 10.1038/s41582-020-0311-0. Epub 2020 Feb 25.

Abstract

Spinal cord injury (SCI) remains one of the biggest challenges in the development of neuroregenerative therapeutics. Cell transplantation is one of numerous experimental strategies that have been identified and tested for efficacy at both preclinical and clinical levels in recent years. In this Review, we briefly discuss the state of human olfactory cell transplantation as a therapy, considering both its current clinical status and its limitations. Furthermore, we introduce a mesenchymal stromal cell derived from human olfactory tissue, which has the potential to induce multifaceted reparative effects in the environment within and surrounding the lesion. We argue that no single therapy will be sufficient to treat SCI effectively and that a combination of cell-based, rehabilitation and pharmaceutical interventions is the most promising approach to aid repair. For this reason, we also introduce a novel pharmaceutical strategy based on modifying the activity of heparan sulfate, an important regulator of a wide range of biological cell functions. The multi-target approach that is exemplified by these types of strategies will probably be necessary to optimize SCI treatment.

摘要

脊髓损伤 (SCI) 仍然是神经再生治疗发展中的最大挑战之一。细胞移植是近年来在临床前和临床水平上经过鉴定和测试的众多实验策略之一。在这篇综述中,我们简要讨论了人类嗅细胞移植作为一种治疗方法的现状,既考虑了其当前的临床状况,也考虑了其局限性。此外,我们介绍了一种来源于人嗅组织的间充质基质细胞,它有可能在损伤内和周围的环境中诱导多方面的修复作用。我们认为,没有单一的治疗方法足以有效地治疗 SCI,细胞治疗、康复和药物干预的结合是最有前途的方法来帮助修复。因此,我们还介绍了一种基于修饰肝素硫酸盐活性的新型药物策略,肝素硫酸盐是广泛的生物细胞功能的重要调节剂。这些类型的策略所体现的多靶点方法可能对于优化 SCI 的治疗是必要的。

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