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Menstrual blood-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells 被引量:10
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作者 Xiao-zhou MOU Jian LIN +6 位作者 Jin-yang CHEN Yi-fei LI Xiao-xing WU Bing-yu XIANG Cai-yun LI Ju-ming MA Charlie XIANG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2013年第11期961-972,共12页
Orthotopic liver transplantation(OLT)is the only proven effective treatment for both end-stage and metabolic liver diseases.Hepatocyte transplantation is a promising alternative for OLT,but the lack of available donor... Orthotopic liver transplantation(OLT)is the only proven effective treatment for both end-stage and metabolic liver diseases.Hepatocyte transplantation is a promising alternative for OLT,but the lack of available donor livers has hampered its clinical application.Hepatocyte-like cells(HLCs)differentiated from many multi-potential stem cells can help repair damaged liver tissue.Yet almost suitable cells currently identified for human use are difficult to harvest and involve invasive procedures.Recently,a novel mesenchymal stem cell derived from human menstrual blood(MenSC)has been discovered and obtained easily and repeatedly.In this study,we examined whether the MenSCs are able to differentiate into functional HLCs in vitro.After three weeks of incubation in hepatogenic differentiation medium containing hepatocyte growth factor(HGF),fibroblast growth factor-4(FGF-4),and oncostain M(OSM),cuboidal HLCs were observed,and cells also expressed hepatocyte-specific marker genes including albumin(ALB),α-fetoprotein(AFP),cytokeratin 18/19(CK18/19),and cytochrome P450 1A1/3A4(CYP1A1/3A4).Differentiated cells further demonstrated in vitro mature hepatocyte functions such as urea synthesis,glycogen storage,and indocyanine green(ICG)uptake.After intrasplenic transplantation into mice with 2/3 partial hepatectomy,the MenSC-derived HLCs were detected in recipient livers and expressed human ALB protein.We also showed that MenSC-derived HLC transplantation could restore the serum ALB level and significantly suppressed transaminase activity of liver injury animals.In conclusion,MenSCs may serve as an ideal,easily accessible source of material for tissue engineering and cell therapy of liver tissues. 展开更多
关键词 menstrual blood-derived mesenchymal stem cell(MenSC) Differentiation HEPATOCYTE Intrasplenic transplantation Partial hepatectomy
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Mini-review:Plasticity of human menstrual blood stem cells derived from the endometrium 被引量:6
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作者 Jian LIN Dennis XIANG +2 位作者 Jin-long ZHANG Julie ALLICKSON Charlie XIANG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2011年第5期372-380,共9页
Stem cells can be obtained from women's menstrual blood derived from the endometrium.The cells display stem cell markers such as Oct-4,SSEA-4,Nanog,and c-kit(CD117),and have the potent ability to differentiate int... Stem cells can be obtained from women's menstrual blood derived from the endometrium.The cells display stem cell markers such as Oct-4,SSEA-4,Nanog,and c-kit(CD117),and have the potent ability to differentiate into various cell types,including the heart,nerve,bone,cartilage,and fat.There has been no evidence of teratoma,ectopic formation,or any immune response after transplantation into an animal model.These cells quickly regenerate after menstruation and secrete many growth factors to display recurrent angiogenesis.The plasticity and safety of the acquired cells have been demonstrated in many studies.Menstrual blood-derived stem cells(MenSCs) provide an alternative source of adult stem cells for research and application in regenerative medicine.Here we summarize the multipotent properties and the plasticities of MenSCs and other endometrial stem cells from recent studies conducted both in vitro and in vivo. 展开更多
关键词 menstrual blood-derived stem cells(menscs) Endometrium MULTIPOTENT PLASTICITY
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琥珀散对人MenSCs植入式子宫内膜异位症裸鼠异位病灶及Beclin1、ZEB1表达的影响 被引量:4
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作者 张悦健 何甜甜 +7 位作者 林陶秀 霍超越 杨思晨 高路益 杨梦萍 罗伯茨宋泽 李长香 马小娜 《药物评价研究》 CAS 2023年第2期294-304,共11页
目的探究琥珀散对人经血源间充质干细胞(MenSCs)植入式子宫内膜异位症(EMT)裸鼠的异位病灶及Bcl-2同源结构域蛋白抗体(Beclin1)、锌指E盒同源结合蛋白1(ZEB1)表达的影响。方法将裸鼠随机分为对照组、模型组、地诺孕素(0.001 g·kg^(... 目的探究琥珀散对人经血源间充质干细胞(MenSCs)植入式子宫内膜异位症(EMT)裸鼠的异位病灶及Bcl-2同源结构域蛋白抗体(Beclin1)、锌指E盒同源结合蛋白1(ZEB1)表达的影响。方法将裸鼠随机分为对照组、模型组、地诺孕素(0.001 g·kg^(-1))组和琥珀散(29 g·kg^(-1))组,每组10只。从EMT患者及健康女性的月经血中提取MenSCs,并借助成脂、成骨诱导分化鉴定其干细胞属性。将EMT MenSCs注射至裸鼠腹部皮下,制备EMT裸鼠模型,对照组植入正常人MenSCs。至第7天每组随机抽取1只裸鼠,开腹观察异位病灶生长情况,并借助HE染色和人类白细胞抗原A(HLAA)免疫荧光法评价模型。自造模成功连续给药21 d,末次给药后第2日取材,观测EMT异位病灶体积及血管分布;切取异位病灶组织,应用实时荧光定量PCR(qRT-PCR)、Western blotting、免疫组织化学及免疫荧光技术分别测定组织中Beclin1与ZEB1在mRNA及蛋白水平的表达。结果EMT源及正常MenSCs为长梭形,呈辐射状向周边集落扩散,且经成脂、成骨诱导分化后均有脂滴、钙结节形成。造模7 d后,对照组未见异位病灶形成,其余各组均有囊泡样病灶形成,且周围血管形成丰富,病理切片均可见子宫内膜腺体和间质,HLAA均阳性表达。与模型组比较,琥珀散能显著缩小EMT裸鼠异位病灶体积(P<0.001),改善周围血管分布。在mRNA水平,与模型组比较,地诺孕素组和琥珀散组ZEB1表达显著降低(P<0.001),Beclin1表达显著升高(P<0.001)。在蛋白水平,与模型组比较,Westernblotting结果显示,地诺孕素组和琥珀散组ZEB1表达显著降低(P<0.05),Beclin1表达显著升高(P<0.01、0.001);免疫组化结果显示,琥珀散组Beclin1大量分布在异位内膜、腺腔以及腺上皮细胞与间质细胞的胞核及胞浆中,Beclin1表达显著增加(P<0.01);免疫荧光结果显示,琥珀散组ZEB1蛋白在异位内膜、腺腔、腺上皮细胞及周围间质细胞的胞核与胞浆中的分布均明显减少,地诺孕素组、琥珀散组ZEB1蛋白表达阳性率显著降低(P<0.001)。结论琥珀散可能通过上调Beclin1、下调ZEB1表达,缩小EMT裸鼠异位病灶,改善周围血管分布。 展开更多
关键词 子宫内膜异位症 经血源间充质干细胞 琥珀散 异位病灶 BECLIN1 ZEB1
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子宫内膜异位症患者与健康女性的经血源间充质干细胞自噬功能比较研究 被引量:3
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作者 张悦健 林陶秀 +5 位作者 何甜甜 杨思晨 李长香 睢丛璐 郭亚楠 马小娜 《药物评价研究》 CAS 2023年第7期1417-1423,共7页
目的比较子宫内膜异位症(EMT)患者与健康女性的经血源间充质干细胞(MenSCs)的自噬功能。方法分别从EMT患者及健康女性的月经血中提取EMT MenSCs(E-MenSCs)和正常MenSCs(H-MenSCs),并借助成脂、成骨诱导分化鉴定其干细胞属性。通过CCK-8... 目的比较子宫内膜异位症(EMT)患者与健康女性的经血源间充质干细胞(MenSCs)的自噬功能。方法分别从EMT患者及健康女性的月经血中提取EMT MenSCs(E-MenSCs)和正常MenSCs(H-MenSCs),并借助成脂、成骨诱导分化鉴定其干细胞属性。通过CCK-8法比较E-MenSCs和H-MenSCs在12、24、48、72、96、120 h时刻于波长450 nm的吸光度(A)值,并绘制细胞增殖曲线,比较2组细胞的细胞活力;运用透射电镜观察E-MenSCs与H-MenSCs的细胞形态,检测比较其中自噬体和自噬溶酶体的数量;采用Western blotting法检测E-MenSCs和H-MenSCs中自噬标志物微管相关蛋白轻链3-II(LC3-II)和Beclin1的蛋白表达。结果E-MenSCs和H-MenSCs均为长梭形,呈辐射状扩散,且经成脂、成骨诱导分化后均有脂滴、钙结节形成。与H-MenSCs比较,E-MenSCs在72、96、120 h的细胞活力均显著升高(P<0.01、0.001),自噬体和自噬溶酶体数量显著减少(P<0.05、0.01),且LC3-Ⅱ、Beclin1蛋白表达量也显著降低(P<0.05)。结论与H-MenSCs比较,E-MenSCs的自噬功能减弱,这可能是EMT发病进展的潜在机制。 展开更多
关键词 子宫内膜异位症 经血源间充质干细胞 自噬 自噬体 自噬溶酶体 BECLIN1 LC3-Ⅱ
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琥珀散通过LncRNA MALAT1/miR-142-3p促进自噬缩小子宫内膜异位症裸鼠异位病灶的机制 被引量:2
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作者 张悦健 林陶秀 +6 位作者 何甜甜 霍超越 高路益 杨思晨 杨梦萍 罗伯茨宋泽 马小娜 《中华中医药杂志》 CAS CSCD 北大核心 2023年第9期4142-4147,共6页
目的:观察琥珀散对子宫内膜异位症(EMT)裸鼠异位病灶的干预作用,并从LncRNA MALAT1/miR-142-3p介导自噬研究其作用机制。方法:将30只7周龄雌性免疫缺陷小鼠随机分为模型组、琥珀散组(29 g/kg)与地诺孕素组(0.001 g/kg),每组10只。从5例... 目的:观察琥珀散对子宫内膜异位症(EMT)裸鼠异位病灶的干预作用,并从LncRNA MALAT1/miR-142-3p介导自噬研究其作用机制。方法:将30只7周龄雌性免疫缺陷小鼠随机分为模型组、琥珀散组(29 g/kg)与地诺孕素组(0.001 g/kg),每组10只。从5例寒凝血瘀型EMT患者月经血中提取经血源间充质干细胞(MenSCs)以制备人MenSCs植入式EMT裸鼠模型。采用HE染色法及人类白细胞抗原α(HLAA)免疫荧光法评价模型。造模成功后连续给药21 d。实时荧光定量PCR和免疫印迹法测定各组异位病灶组织中LncRNA MALAT1、miR-142-3p及自噬标志分子(Beclin1和LC3Ⅱ)的表达情况。结果:造模后,3组注射区均有囊泡样组织形成,病理切片见子宫内膜腺体和间质,免疫荧光示HLAA阳性,系造模成功。与模型组比较,琥珀散组异位病灶体积显著缩小(P<0.01),LncRNA MALAT1和Beclin1的RNA水平、Beclin1和LC3Ⅱ蛋白水平均显著升高(P<0.01,P<0.05),miR-142-3p被显著抑制(P<0.01)。结论:琥珀散能明显缩小EMT裸鼠异位病灶体积,其作用机制可能是其促进LncRNA MALAT1诱骗miR-142-3p以上调Beclin1进而增强异位内膜自噬。 展开更多
关键词 子宫内膜异位症 琥珀散 竞争性内源RNA LncRNA MALAT1 miR-142-3p 自噬 经血源间充质干细胞 异位病灶 机制
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