Center for Craniofacial Molecular Biology, University of Southern California, School of Dentistry, Los Angeles, CA 90033, USA.
J Immunol. 2009 Dec 15;183(12):7787-98. doi: 10.4049/jimmunol.0902318.
Aside from the well-established self-renewal and multipotent differentiation properties, mesenchymal stem cells exhibit both immunomodulatory and anti-inflammatory roles in several experimental autoimmune and inflammatory diseases. In this study, we isolated a new population of stem cells from human gingiva, a tissue source easily accessible from the oral cavity, namely, gingiva-derived mesenchymal stem cells (GMSCs), which exhibited clonogenicity, self-renewal, and multipotent differentiation capacities. Most importantly, GMSCs were capable of immunomodulatory functions, specifically suppressed peripheral blood lymphocyte proliferation, induced expression of a wide panel of immunosuppressive factors including IL-10, IDO, inducible NO synthase (iNOS), and cyclooxygenase 2 (COX-2) in response to the inflammatory cytokine, IFN-gamma. Cell-based therapy using systemic infusion of GMSCs in experimental colitis significantly ameliorated both clinical and histopathological severity of the colonic inflammation, restored the injured gastrointestinal mucosal tissues, reversed diarrhea and weight loss, and suppressed the overall disease activity in mice. The therapeutic effect of GMSCs was mediated, in part, by the suppression of inflammatory infiltrates and inflammatory cytokines/mediators and the increased infiltration of regulatory T cells and the expression of anti-inflammatory cytokine IL-10 at the colonic sites. Taken together, GMSCs can function as an immunomodulatory and anti-inflammatory component of the immune system in vivo and is a promising cell source for cell-based treatment in experimental inflammatory diseases.
除了已被证实的自我更新和多能分化特性外,间充质干细胞在几种实验性自身免疫和炎症性疾病中还具有免疫调节和抗炎作用。在这项研究中,我们从人体牙龈中分离出一种新的干细胞群体,即牙龈来源的间充质干细胞(GMSCs),它具有克隆形成能力、自我更新和多能分化能力。最重要的是,GMSCs 具有免疫调节功能,能够在炎症细胞因子 IFN-γ的刺激下,抑制外周血淋巴细胞增殖,并诱导表达广泛的免疫抑制因子,包括 IL-10、IDO、诱导型一氧化氮合酶(iNOS)和环氧化酶 2(COX-2)。通过系统输注 GMSCs 进行细胞治疗,可显著改善实验性结肠炎的临床和组织病理学严重程度,修复受损的胃肠道黏膜组织,逆转腹泻和体重减轻,并抑制小鼠的整体疾病活动。GMSCs 的治疗效果部分是通过抑制炎症浸润和炎症细胞因子/介质,增加调节性 T 细胞的浸润和抗炎细胞因子 IL-10 在结肠部位的表达来介导的。总之,GMSCs 可以作为体内免疫系统的免疫调节和抗炎成分,是实验性炎症性疾病细胞治疗的有前途的细胞来源。