Zhou Yi-Kun, Zhu Ling-Su, Huang Hua-Ming, Cui Sheng-Jie, Zhang Ting, Zhou Yan-Heng, Yang Rui-Li
Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China.
Department of Orthodontics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China.
World J Stem Cells. 2020 Dec 26;12(12):1623-1639. doi: 10.4252/wjsc.v12.i12.1623.
Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide, which emphasizes the urgent need to identify novel treatments. Stem cells from human exfoliated deciduous teeth (SHED), which are easy to obtain in a non-invasive manner, show pronounced proliferative and immunomodulatory capacities.
To investigate the protective effects of SHED on concanavalin A (ConA)-induced hepatitis in mice, and to elucidate the associated regulatory mechanisms.
We used a ConA-induced acute hepatitis mouse model and an co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis, as well as the associated underlying mechanisms.
SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3, CD4, tumor necrosis-alpha, and interferon-gamma inflammatory cells. Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice. SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations. Mechanistically, ConA upregulated tumor necrosis-alpha and interferon-gamma expression, which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from ConA-induced apoptosis.
SHED alleviates ConA-induced acute liver injury inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway. Our findings could provide a potential treatment strategy for hepatitis.
自身免疫性肝炎是一种严重威胁全球人类健康的自身免疫性肝病，这凸显了识别新治疗方法的迫切需求。人脱落乳牙干细胞（SHED）易于以非侵入性方式获取，具有显著的增殖和免疫调节能力。
研究SHED对刀豆蛋白A（ConA）诱导的小鼠肝炎的保护作用，并阐明相关的调节机制。
我们使用ConA诱导的急性肝炎小鼠模型和共培养系统来研究SHED对ConA诱导的自身免疫性肝炎的保护作用以及相关的潜在机制。
输注SHED可预防由ConA诱导的CD3、CD4、肿瘤坏死因子-α和干扰素-γ炎性细胞浸润所导致的异常肝脏组织病理学结构。肝炎小鼠的丙氨酸氨基转移酶和天冬氨酸氨基转移酶显著升高。因此，输注SHED可阻止ConA诱导的丙氨酸氨基转移酶和天冬氨酸氨基转移酶升高。从机制上讲，ConA上调肿瘤坏死因子-α和干扰素-γ的表达，其通过核因子-κB途径被激活以诱导肝细胞凋亡，从而导致急性肝损伤。给予SHED可保护肝细胞免受ConA诱导的凋亡。
SHED通过抑制核因子-κB途径介导的肝细胞凋亡减轻ConA诱导的急性肝损伤。我们的研究结果可为肝炎提供一种潜在的治疗策略。
