Umbilical cord mesenchymal stem cells limit post-stroke infection

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.