Umbilical cord mesenchymal stem cells limit post-stroke infection

Jianbang Han, Yuanlong Xie, Z. Feng, Haitao Sun, Feng Li, Q. Ouyang, Zhongfei Zhang, Xiaoxiong Zou, Ying‐qian Cai, Yu-xi Zou, Y. Tang, Xiaodan Jiang
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Abstract

Background Brain ischemia leads to excessive infiltration of clusters of CD8+ T and natural killer (NK) cells in the brain, which aggravate ischemic brain injury. Acute ischemic stroke also has a negative impact on the antibacterial immune response, leading to stroke-induced immunodepression and infection. Umbilical cord mesenchymal stem cell (ucMSC) have an immunosuppressive function. Therefore, we aimed to determine whether ucMSC treatment alleviates the excessive infiltration of CD8+ T and NK cells. We also investigated significant concerns that ucMSC treatment might suppress antimicrobial immunity, leading to an increased risk of infection. Methods After middle cerebral artery occlusion, stroke and post-stroke infective mice received intravenous injection of ucMSC. We performed haematoxylin and eosin staining of organs and assessed the Modified Neurological Severity Score (mNSS),the activated state of microglia,quantity and distribution of CD8 + T and NK cells. Changes of cytokines (IL-6, TNF-α, IL-10), and blood biochemical indexes were also detected.We then assessed autophagy and apoptosis of platelets, as well as mitochondrial membrane potential (MMP) and ATP levels.In vitro ucMSC was co-cultured with platelet and Escherichia coli, followed by detection of the E. coli growth curve. Results ucMSC treatment ameliorated the infiltration of CD8+ T and NK cells in the brain, reduced levels of proinflammatory cytokines, and increased anti-inflammatory cytokines.ucMSC treatment limit post-stroke infection and reduce the inflmamatory injury of various organs induced by post-stroke infection,as well as ucMSC inhibit the growth of Escherichia coli in vivo and vitro.ucMSC treatment maintained autophagy, MMP, and the production of ATP, while inhibiting apoptosis of platelets in vivo. Conclusions Based on these findings, ucMSC may represent a potential and safe therapeutic option for stroke treatment by inhibiting brain injury and limiting post-stroke infection.
脐带间充质干细胞限制中风后感染
脑缺血导致CD8+ T和NK细胞簇在脑内过度浸润,加重了缺血性脑损伤。急性缺血性脑卒中对抗菌免疫反应也有负面影响,导致脑卒中诱导的免疫抑制和感染。脐带间充质干细胞(ucMSC)具有免疫抑制功能。因此,我们的目的是确定ucMSC治疗是否能缓解CD8+ T和NK细胞的过度浸润。我们还调查了ucMSC治疗可能抑制抗菌免疫,导致感染风险增加的重大担忧。方法脑卒中小鼠和脑卒中后感染小鼠经大脑中动脉闭塞后静脉注射ucMSC。我们对器官进行了苏木精和伊红染色,并评估了改良神经严重程度评分(mNSS)、小胶质细胞的激活状态、CD8 + T和NK细胞的数量和分布。检测各组细胞因子(IL-6、TNF-α、IL-10)及血液生化指标的变化。然后,我们评估了血小板的自噬和凋亡,以及线粒体膜电位(MMP)和ATP水平。将体外培养的ucMSC与血小板和大肠杆菌共培养,检测大肠杆菌生长曲线。结果骨髓间充质干细胞治疗可改善脑内CD8+ T和NK细胞的浸润,降低促炎细胞因子水平,增加抗炎细胞因子水平。ucMSC治疗可以限制脑卒中后感染,减轻脑卒中后感染引起的各脏器炎症损伤,并抑制体内外大肠杆菌的生长。ucMSC处理维持了自噬、MMP和ATP的产生,同时抑制了血小板的凋亡。基于这些发现,ucMSC可能通过抑制脑损伤和限制脑卒中后感染,为卒中治疗提供了一种潜在且安全的治疗选择。
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