Huang Feng, Chen Maogen, Chen Weiqian, Gu Jian, Yuan Jia, Xue Yaoqiu, Dang Junlong, Su Wenru, Wang Julie, Zadeh Homayoun H, He Xiaoshun, Rong Limin, Olsen Nancy, Zheng Song Guo
Department of Clinical Immunology, Third Affiliated Hospital at Sun Yat-sen University , Guangzhou , China.
Organ Transplant Center, First Affiliated Hospital at Sun Yat-sen University , Guangzhou , China.
Front Immunol. 2017 Feb 2;8:68. doi: 10.3389/fimmu.2017.00068. eCollection 2017.
Mesenchymal stem cells have the capacity to maintain immune homeostasis and prevent autoimmunity. We recently reported that human-derived gingival mesenchymal stem cells (GMSCs) have strong capacity to suppress immune responses and T cell-mediated collagen-induced arthritis in animals. However, it is unclear whether these cells can suppress human T cell-mediated diseases. Here, we used a xenogenic GVHD model in the NOD/SCID mouse, which is a useful preclinical construct for evaluating the therapeutic and translational potential of this approach for applications in human disease. We found that GMSCs potently suppressed the proliferation of PBMC and T cells . Co-transfer of GMSC with human PBMC significantly suppressed human cell engraftment and markedly prolonged the mouse survival. Moreover, we demonstrated that GMSCs inhibited human PBMC-initiated xenogenic responses CD39/CD73/adenosine and IDO signals. These findings suggest the potential for GMSCs to suppress human immune responses in immune system-mediated diseases, offering a potential clinical option to be used for modulating GVHD and autoimmune diseases.
间充质干细胞具有维持免疫稳态和预防自身免疫的能力。我们最近报道，人源牙龈间充质干细胞（GMSCs）在动物体内具有强大的抑制免疫反应和T细胞介导的胶原诱导性关节炎的能力。然而，尚不清楚这些细胞是否能抑制人类T细胞介导的疾病。在此，我们在NOD/SCID小鼠中使用了异种移植物抗宿主病（GVHD）模型，这是一种用于评估该方法在人类疾病中的治疗和转化潜力的有用临床前构建体。我们发现GMSCs能有效抑制外周血单核细胞（PBMC）和T细胞的增殖。GMSCs与人PBMC的共同移植显著抑制了人类细胞的植入，并显著延长了小鼠的存活时间。此外，我们证明GMSCs通过CD39/CD73/腺苷和吲哚胺2,3-双加氧酶（IDO）信号抑制人PBMC引发的异种反应。这些发现表明GMSCs在免疫系统介导的疾病中具有抑制人类免疫反应的潜力，为用于调节GVHD和自身免疫性疾病提供了一种潜在的临床选择。
