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《醫(yī)學(xué)畢業(yè)論文人基質(zhì)細(xì)胞衍生因子1對(duì)骨髓間充質(zhì)干細(xì)胞增殖的影響》由會(huì)員上傳分享,免費(fèi)在線閱讀,更多相關(guān)內(nèi)容在學(xué)術(shù)論文-天天文庫(kù)。
1、人基質(zhì)細(xì)胞衍生因子1對(duì)骨髓間充質(zhì)干細(xì)胞增殖的影響姓名:2014年6月25日人基質(zhì)細(xì)胞衍生因子1對(duì)骨髓間充質(zhì)干細(xì)胞增殖的影響作者:孔霞,唐俊明,郭凌鄖,楊建業(yè),陳龍,黃永章,王家寧【摘要】目的:探索人基質(zhì)細(xì)胞衍生因子1(SDF1)對(duì)間充質(zhì)干細(xì)胞(MSC)增殖的影響.方法:采用經(jīng)典的全骨髓貼壁法培養(yǎng)MSC,通過(guò)成骨、成脂肪等多向誘導(dǎo)分化以及流式細(xì)胞儀分析其表面標(biāo)記(CD133,CD34,CD90,CD105)等鑒定MSC特征;以P3MSC為實(shí)驗(yàn)材料,采用H3TdR參入法分析SDF1對(duì)MSC增殖的影響.以50nmol/L渥曼青霉
2、素,10mmol/LLY294002,50mmol/LPD98059,0.1g/LAMD3100等分別處理P3MSC,觀察SDF1影響MSC±汽殖的信號(hào)機(jī)制.結(jié)果:培養(yǎng)的MSC呈現(xiàn)出CXCR4,CD90和CD105強(qiáng)陽(yáng)性,具有成骨、成脂肪等多向分化能力;含有100mg/LSDF1的20mL/L促進(jìn)了MSC增殖,而含有100mg/LSDF1的150mL/LFBS抑制了MSC增殖.SDF1抑制MSC增殖的效應(yīng)與其使MSC停滯在G1/S期有關(guān).促分裂原活化蛋白激酶P38MAPK阻斷劑SB203580和CXCR4阻斷劑AMD310
3、0取消了SDF1抑制MSC增殖的效應(yīng),而細(xì)胞外信號(hào)調(diào)節(jié)激酶阻斷劑PD98059加強(qiáng)了SDF1抑制MSC增殖的效應(yīng).結(jié)論:SDF1/CXCR4介導(dǎo)的抑制MSC增殖的效應(yīng)與促分裂原活化蛋白激酶和細(xì)胞外信號(hào)調(diào)節(jié)激酶等信號(hào)分子有關(guān).【關(guān)鍵詞】人基質(zhì)細(xì)胞源衍生因子1;間充質(zhì)干細(xì)胞;增殖;促分裂原活化蛋白激酶【Abstract】AIM:Toexploretheeffectofstromalcellderivedfactor1alpha(SDF-la)onmesenchymalstemcell(MSC)proliferation.MET
4、HODS:MSCculturewasperformedwiththeclassicalwholebonemarrowadheringmethod;MSCwasidentifiedthroughmultidifferentiationandsurfacemarkerassay(CXCR4,CD133,CD34,CD90,CD105);AfterMSCsweretreatedwith100mg/LSDFla,50nmol/Lwortmannin,10mmol/LLY294002,50mmol/LPD98059and0.1g/L
5、AMD3100inhibitors,theproliferationratesweremeasuredby[3H]thymidineincorporationassay.RESULTS:CulturedMSCshadtheabilityofmultidifferentiationandhighlyexpressedCXCR4,CD105andCD90.20mL/LFBSincluding100mg/LSDFlapromotedMSCproliferation,howeverexposureofMSCsto150mL/LFB
6、Sincluding100mg/LSDFlacouldinducemarkedinhibitionofMSCproliferationthroughthearrestintheGl/Scheckpoint.AnditsinhibitoryeffectonMSCproliferationwaspartlyreversedbyp38mitogenactivatedproteinkinase(MAPK)inhibitorSB203580andCXCR4inhibitorAMD3100.Howeveritsinhibitionef
7、fectonMSCproliferationwasobviouslyenhancedbyextracellularsignalregulatedkinase(ERK1/2)inhibitorPD98059.CONCLUSION:TheeffectofSDFlaonMSCproliferationisrelatedtoERK1/2andp38MAPK.【Keywords】hSDFla;mesenchymalstemcell;proliferation;MAPK0引言骨髓來(lái)源的間充質(zhì)丁?細(xì)胞(bonemarrowmesench
8、ymalstemcell,MSC)在一定條件下可以分化為心肌、成骨、軟骨、脂肪、胰島、肌腱等多種類型的細(xì)胞[1].在心肌內(nèi)、靜脈內(nèi)、冠脈內(nèi)等不同途徑移植MSC或粒系集落刺激因子動(dòng)員骨髓發(fā)現(xiàn)其可以辻移到心肌梗死部位,通過(guò)參與血管新生、心肌再生等改善修復(fù)受損的心臟[1].有研究[2]發(fā)現(xiàn),SDF1/CXCR