美国斯坦福大学医学院Wernig, Marius课题组在研究中取得进展。他们的最新研究揭示了髓样细胞替代对慢性实验性自身免疫性脑脊髓炎具有神经保护作用。这一研究成果发表在2024年3月21日出版的国际学术期刊《自然—神经科学》上。

利用单核RNA测序，该课题组人员鉴定了慢性实验性自身免疫性脑炎(EAE)中，与神经保护和免疫抑制相关的反应性骨髓细胞状态。EAE小鼠的自体造血细胞移植导致神经保护髓细胞状态的增加、神经功能缺陷的改善、脱髓鞘病变数量的减少，效应T细胞与反应性星形胶质细胞增生的改善。改良的自体造血细胞移植后增强髓细胞整合，进一步改善了这些神经保护作用。这些数据表明，髓细胞操控或替代可能是慢性中枢神经系统炎症的有效治疗策略。

研究人员表示，多发性硬化(MS)是一种以中枢神经系统(CNS)脱髓鞘为特征的自身免疫性疾病。在开放标签临床研究中，自体造血细胞移植(HCT)显示出治疗缓解型多发性硬化症的良好疗效，但其治疗效果的细胞机制尚不清楚。

附：英文原文

Title: Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis

Author: Mader, Marius Marc-Daniel, Napole, Alan, Wu, Danwei, Atkins, Micaiah, Scavetti, Alexa, Shibuya, Yohei, Foltz, Aulden, Hahn, Oliver, Yoo, Yongjin, Danziger, Ron, Tan, Christina, Wyss-Coray, Tony, Steinman, Lawrence, Wernig, Marius

Issue&Volume: 2024-03-21

Abstract: Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination of the central nervous system (CNS). Autologous hematopoietic cell transplantation (HCT) shows promising benefits for relapsing–remitting MS in open-label clinical studies, but the cellular mechanisms underlying its therapeutic effects remain unclear. Using single-nucleus RNA sequencing, we identify a reactive myeloid cell state in chronic experimental autoimmune encephalitis (EAE) associated with neuroprotection and immune suppression. HCT in EAE mice results in an increase of the neuroprotective myeloid state, improvement of neurological deficits, reduced number of demyelinated lesions, decreased number of effector Tcells and amelioration of reactive astrogliosis. Enhancing myeloid cell incorporation after a modified HCT further improved these neuroprotective effects. These data suggest that myeloid cell manipulation or replacement may be an effective therapeutic strategy for chronic inflammatory conditions of the CNS.

DOI: 10.1038/s41593-024-01609-3

Source: https://www.nature.com/articles/s41593-024-01609-3