Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis.
Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis.
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DOI：
10.4049/jimmunol.0902318
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发表时间：
2009-12-15
期刊：
影响因子：
--
通讯作者：
Le AD
中科院分区：
文献类型：
--
作者：
Zhang Q;Shi S;Liu Y;Uyanne J;Shi Y;Shi S;Le AD
除了良好的自我更新和多潜能分化特性，间充质干细胞在几种实验性自身免疫性和炎症性疾病中显示出免疫调节和抗炎作用。在这项研究中，我们从人牙龈中分离出了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、自我更新和多向分化的能力。最重要的是，GMSCs具有免疫调节功能，特别是抑制外周血淋巴细胞增殖，诱导多种免疫抑制因子的表达，包括IL-10、iDO、诱导型一氧化氮合酶(INOS)和环氧合酶-2(COX-2)，以应答炎症细胞因子干扰素-γ。系统输注GMSCs细胞治疗实验性结肠炎可明显改善小鼠结肠炎的临床和组织病理学严重程度，恢复受损的胃肠黏膜组织，逆转腹泻和体重减轻，并抑制整体疾病活动。GMSCs的治疗作用部分是通过抑制炎性细胞浸润和炎性细胞因子/介质，增加调节性T细胞在结肠部位的浸润和抗炎细胞因子IL-10的表达而实现的。综上所述，GMSCs在体内可以作为免疫系统的免疫调节和抗炎成分发挥作用，是实验性炎症性疾病细胞治疗的一种有前途的细胞来源。
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-γ. 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.
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