CAJ | 학술논문

目的探讨人羊膜间充质干细胞(hAMSCs)对1型糖尿病的疗效及免疫调节作用.方法分离培养hAMSCs;建立大鼠1型糖尿病模型,分为正常组、模型组、培养基组、hAMSCs组和胰岛素组,每组6只.hAMSCs组经舌下静脉注射5×106个hAMSCs,动态监测血糖水平,检测血浆胰岛素浓度,观察胰腺病理变化和hAMSCs在胰腺中的分布,分析hAMSCs表型和淋巴细胞亚群,测定血浆Th1、Th2型细胞因子.结果与模型组比较,hAMSCs组血糖水平明显下降,血浆胰岛素含量增加,胰腺病损程度减轻;移植后6周,hAMSCs组外周血Th1和Th17细胞百分比下降(均P＜0.05),而Th2细胞和FoxP3+ Treg细胞上调(均P＜0.01);血浆Th1型细胞因子干扰素-γ、肿瘤坏死因子-α和白细胞介素(IL)-2的浓度下降(均P＜0.01),Th2型细胞因子IL-4升高(P＜0.05);hAMSCs组胰腺组织中未见由hAMSCs分化的胰岛素分泌细胞.结论 hAMSCs能明显降低1型糖尿病大鼠血糖和减轻胰岛损伤,其作用机制可能主要与上调Fox P3+ Treg有关.
목적 탐토인양막간충질간세포(hAMSCs)대1형당뇨병적료효급면역조절작용.방법 분리배양hAMSCs;건립대서1형당뇨병모형,분위정상조、모형조、배양기조、hAMSCs조화이도소조,매조6지.hAMSCs조경설하정맥주사5×106개hAMSCs,동태감측혈당수평,검측혈장이도소농도,관찰이선병리변화화hAMSCs재이선중적분포,분석hAMSCs표형화림파세포아군,측정혈장Th1、Th2형세포인자.결과 여모형조비교,hAMSCs조혈당수평명현하강,혈장이도소함량증가,이선병손정도감경;이식후6주,hAMSCs조외주혈Th1화Th17세포백분비하강(균P＜0.05),이Th2세포화FoxP3+ Treg세포상조(균P＜0.01);혈장Th1형세포인자간우소-γ、종류배사인자-α화백세포개소(IL)-2적농도하강(균P＜0.01),Th2형세포인자IL-4승고(P＜0.05);hAMSCs조이선조직중미견유hAMSCs분화적이도소분비세포.결론 hAMSCs능명현강저1형당뇨병대서혈당화감경이도손상,기작용궤제가능주요여상조Fox P3+ Treg유관.
Objective To study the therapeutic effect and immunologic regulation of human amniotic mesenchymal stem cells (hAMSCs) in rats with experimental type 1 diabetes mellitus (T1DM).Methods The hAMSCs from human amnion were isolated and cultured in vitro,then phenotype was analyzed by flow cytometry.T1DM were produced by administering streptozocin to rats.The rats were divided into normal control group (n =6),T1 DM model group (n =6),medium treated group (n =6),hAMSCs transplanted group(n =6),and insulin treated group(n =6).5 × 106of hAMSCs or vehicle were administered to rats via sublingual vein.Blood glucose levels of rats were recorded weekly in the groups for six weeks by Blood Sugar Meter.At the end of 6 weeks after hAMSCs transplantation,concentrations of plasma insulin were detected by ELISA; histopathological changes of pancreas,surviwl and differentiation of transplanted hAMSCs in pancreatic tissue were studied with HE staining,and immunofluorescence staining; percentages of lymphocyte subsets in peripheral blood mononuclear cells were determined by flow cytometry ; concentrations of plasma cytokines were determined by cytometric bead array.Results After hAMSCs transplantation,blood glucose levels in rats with T1DM were decreased (P ＜ 0.01),while concentrations of plasma insulin were increased significantly (P＜0.01).At 6 weeks,cell-treated animals showed an improvement in pancreas damage ; the percentages of CD4 + IFN-γ+ (Th 1) and C D4 + interleukin (IL)-17 + (Th 17) cells were reduced (all P＜0.05),while the percentages of FoxP3-positive regulatory T cells (FoxP3 +Treg) and CD4+ IL-4+(Th2) cells were increased (all P＜0.01) ; plasma concentrations of interferon-γ,IL-2,and tumor necrosis factor-αwere decreased (all P＜0.01),but IL-4 level was increased (P＜0.05).No histological evidence of insulin producing cells from hAMSCs was seen within pancreas.Conclusions hAMSCs may reduce blood glucose and alleviate the islet damage in rats with T1 DM,which is related to their potential to up-regulate FoxP3 +Treg cells.