用于治疗移植物抗宿主病的间充质干细胞衍生的外泌体:更新的观点。
Mesenchymal stem cell-derived exosomes for managing graft-versus-host disease: An updated view.
发表日期:2023 Nov 05
作者:
Zahra Shafeghat, Maryam Dorfaki, Shiva Dehrouyeh, Fahime Lavi Arab, Mona Roozbehani, Reza Falak, Fatemeh Faraji, Reza Jafari
来源:
Stem Cell Research & Therapy
摘要:
移植物抗宿主病(GvHD)是干细胞移植后最常见的并发症,也是造血干细胞移植(HSCT)治疗血液肿瘤的主要限制因素之一。 GvHD 是一种全身性炎症性疾病,是由供体 T 细胞识别受体外来抗原引起的。此外,由自身反应性免疫细胞引起的免疫失调使 HSCT 后的强效炎症过程复杂化。虽然没有一种批准的 GvHD 治疗方法,但皮质类固醇是最常见的一线治疗方法。外泌体是直径在30至120nm之间的生物囊泡,其携带多种生物活性分子。已知它们在间充质干细胞的旁分泌作用中发挥关键作用,具有治疗和组织修复作用,包括免疫抑制潜力。外泌体无法自我复制,但由于其体积小和液体状结构,它们可以穿过生理屏障。外泌体相对容易制备,并且可以通过过滤过程快速灭菌。施用源自间充质干细胞的外泌体可有效减轻 GvHD 症状并显着提高 HSCT 受者的存活率。间充质干细胞衍生的外泌体疗法可减轻 HSCT 后患者 GvHD 的临床症状。针对 GvHD 患者的研究表明,间充质干细胞来源的外泌体通过激活的自然杀伤细胞(NK 细胞)抑制 IFN-γ 和 TNF-α 的释放,从而降低 NK 细胞的致死功能和炎症反应。当前的综述提供了关于使用间充质干细胞及其衍生的外泌体治疗 GvHD 的全面概述。版权所有 © 2023。由 Elsevier B.V. 出版。
Graft-versus-host disease (GvHD) is the most common complication after stem cell transplantation, and also it is one of the primary limiting factors for the use of hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic cancers. GvHD, a systemic inflammatory disease, is caused by donor T cells recognizing the recipient's foreign antigens. In addition, an immune dysregulation, caused by autoreactive immune cells, complicates potent inflammatory process following HSCT. While there is no one approved treatment method for GvHD, corticosteroids are the most common first-line treatment. Exosomes are biological vesicles between 30 and 120 nm in diameter, which carry various biologically active molecules. They are known to play a key role in the paracrine effect of mesenchymal stem cells with therapeutic and tissue repair effects, including an immunosuppressive potential. Exosomes are unable to replicate themselves but because of their small size and fluid-like structure, they can pass through physiological barriers. Exosome are relatively easy to prepare and they can be quickly sterilized by a filtration process. Administration of exosomes, derived from mesenchymal stem cells, effectively reduced GvHD symptoms and significantly increased HSCT recipients' survival. Mesenchymal stem cell-derived exosome therapy reduced clinical symptoms of GvHD in patients after HSCT. Studies in patients with GvHD described that that mesenchymal stem cell-derived exosomes inhibited the release of IFN-γ and TNF-α by activated natural killer (NK cells), thereby reducing the lethal function of NK cells and inflammatory responses. Current review provides a comprehensive overview about the use of mesenchymal stem cells and their derived exosomes for the treatment of GvHD.Copyright © 2023. Published by Elsevier B.V.