中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (1): 48-52.doi: 10.4103/1673-5374.314292

• 综述:退行性病与再生 • 上一篇    下一篇

间充质基质细胞作为传染病相关脑病辅助治疗的新观点

  

  • 出版日期:2022-01-05 发布日期:2021-09-18

New perspectives for mesenchymal stromal cells as an adjuvant therapy for infectious disease-associated encephalopathies

Maiara N. Lima1, #, Maria C. Barbosa-Silva1, #, Tatiana Maron-Gutierrez1, 2, *   

  1. 1Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, RJ, Brazil; 2National Institute of Science and Technology on Neuroimmunomodulation, Rio de Janeiro, Brazil
  • Online:2022-01-05 Published:2021-09-18
  • Contact: Tatiana Maron-Gutierrez, PhD, tati.maron@gmail.com or tatiana.maron@ioc.fiocruz.br.
  • Supported by:
    This work was supported by the Brazilian Council for Scientific and Technological Development (grant number 406110/2016-6) and Inova Fiocruz/Oswaldo Cruz Foundation (grant number VPPCB-008-FIO-18-2-56-30; to TMG).

摘要:

Neural Regen Res间充质干细胞释放细胞因子和趋化因子诱导抗炎环境调节免疫系统

对感染相关脑病发病机制的认识仍然非常有限,细胞治疗是神经退行性疾病最有希望的替代方法之一,其在感染性疾病中的应用具有重要意义。间充质干细胞是一种具有巨大免疫调节潜能的细胞,近年来在包括中枢神经系统疾病在内的多种疾病的临床和临床前研究中的应用日益增多。间充质干细胞可以通过多种机制发挥其有益的作用,如直接接触细胞,通过表面受体,也可以通过旁分泌或内分泌机制。旁分泌机制被科学界广泛接受,涉及可溶性因子的释放,包括细胞因子、趋化因子和营养因子以及细胞外小泡。最新研究表明间充质干细胞在脓毒症相关脑病实验模型中的应用。单剂量静脉注射间充质干细胞能够调节全身和脑内的炎症介质,保持血脑屏障的完整性,减少星形胶质细胞增生,改善空间和厌恶性记忆以及焦虑样行为。此外,用脂多糖刺激星形胶质细胞并用间充质干细胞的条件培养基处理的体外实验减少了星形胶质细胞增生,提示了旁分泌作用机制。

来自巴西奥斯瓦尔多科鲁兹研究所的Tatiana Maron-Gutierrez团队认为单剂量的间充质干细胞作为辅助治疗可防止血管损伤和血脑屏障破坏,并改善感染伯氏疟原虫的小鼠的抑郁样行为。与先前对脓毒症的研究相似,间充质干细胞分泌体通过减少乳酸脱氢酶的释放保护血红素(一种与寄生虫代谢有关的分子)刺激的内皮细胞免受细胞损伤/死亡。考虑到间充质干细胞治疗败血症相关性脑病和脑疟疾的有益结果,间充质干细胞治疗其他感染性神经系统并发症在调节急性变化和改善神经系统状况方面有很大的潜力。间充质干细胞可以调节神经炎症。间充质干细胞治疗与常规治疗相结合能有效地减轻神经炎症引起的长期影响,如认知和行为损伤。这些细胞的分泌体,包括生长因子、细胞因子、趋化因子和携带遗传物质的细胞外小泡,参与了保护作用。

    文章在《中国神经再生研究(英文版)》杂志2022年 1 月 1 期发表。

https://orcid.org/0000-0002-6905-2007 (Tatiana Maron-Gutierre); https://orcid.org/0000-0002-9532-1936 (Maiara N. Lima); 
https://orcid.org/0000-0001-6842-9207 (Maria C. Barbosa-Silva)

Abstract: Knowledge of the mechanisms that trigger infection-related encephalopathies is still very limited and cell therapies are one of the most promising alternatives for neurodegenerative diseases, and its application in infectious diseases can be of great relevance. Mesenchymal stromal cells are cells with great immunomodulatory potential; therefore, their use in clinical and preclinical studies in a variety of diseases, including central nervous system diseases, increased in the last decade. Mesenchymal stromal cells can exert their beneficial effects through several mechanisms, such as direct cell contact, through surface receptors, and also through paracrine or endocrine mechanisms. The paracrine mechanism is widely accepted by the scientific community and involves the release of soluble factors, which include cytokines, chemokines and trophic factors, and extracellular vesicles. This mini review discusses mesenchymal stromal cells mechanisms of action in neurological disorders, the neuroinflammatory process that takes place in the brain as a result of peripheral inflammation and changes in the brain’s cellular scenario as a common factor in central nervous system diseases, and mesenchymal stromal cells therapy in encephalopathies. Mesenchymal stromal cells have been shown to act in neuroinflammation processes, leading to improved survival and mitigating behavioral damage. More recently, these cells have been tested in preclinical models of infectious diseases-associated encephalopathies (e.g., cerebral malaria and sepsis associated encephalopathy) and have shown satisfactory results.

Key words: behavior, cell therapy, cognition, encephalopathy, malaria, mesenchymal stromal cell, sepsis