间充质干细胞
CD8型
羊膜
干细胞
外周血单个核细胞
免疫学
T细胞
移植物抗宿主病
造血干细胞移植
免疫抑制
肿瘤坏死因子α
移植
免疫系统
医学
造血
骨髓
癌症研究
生物
病理
内科学
细胞生物学
体外
胎儿
怀孕
生物化学
遗传学
作者
Yoshiyuki Tago,Chiho Kobayashi,Mineko Ogura,Jutaro Wada,Sho Yamaguchi,Takashi Yamaguchi,Masahiro Hayashi,Tomoyuki Nakaishi,Hiroshi Kubo,Yoshiyasu Ueda
标识
DOI:10.1038/s41598-021-81916-y
摘要
Abstract Acute graft-versus-host disease (GVHD) is characterized by severe tissue damage that is a life-threatening complication of allogeneic hematopoietic stem cell transplantation. Due to their immunosuppressive properties, mesenchymal stem cells (MSC) have been increasingly examined for the treatment of immune-related diseases. We aimed to assess the immunosuppressive effects of human amnion-derived MSC (AMSC) in a xenogeneic GVHD NOD/Shi-scid IL2rγnull mouse model using human peripheral blood mononuclear cells (PBMC). Additionally, we used human bone marrow-derived MSC (BMSC) as comparative controls to determine differences in immunomodulatory functions depending on the MSC origin. Administration of AMSC significantly prolonged survival, and reduced human tumor necrosis factor-α (TNF-α) concentration and percentage of programmed cell death protein-1 receptor (PD-1) + CD8 + T cell populations compared with in GVHD control mice. Furthermore, colonic inflammation score and percentage of human CD8 + T cell populations in AMSC-treated mice were significantly lower than in GVHD control and BMSC-treated mice. Interestingly, gene expression and protein secretion of the PD-1 ligands were higher in AMSC than in BMSC. These findings are the first to demonstrate that AMSC exhibit marked immunosuppression and delay acute GVHD progression by preventing T cell activation and proliferation via the PD-1 pathway.
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