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1、神經(jīng)干細(xì)胞向神經(jīng)元分化調(diào)控的研究進(jìn)展岳英杰(綜述)費(fèi)昶張?。▽徯#菊!可窠?jīng)干細(xì)胞是一類具冇分裂潛能和自更新能力的母細(xì)胞,它可以通過(guò)對(duì)稱分裂和不對(duì)稱分裂方式產(chǎn)生神經(jīng)組織的各類細(xì)胞,包括神經(jīng)元、星形膠質(zhì)細(xì)胞和少突膠質(zhì)細(xì)胞。中樞神經(jīng)系統(tǒng)受到損傷后,神經(jīng)元和膠質(zhì)細(xì)胞的損傷導(dǎo)致了臨床癥狀,內(nèi)源性神經(jīng)干細(xì)胞的修復(fù)作用不大,原因是干細(xì)胞的數(shù)量有限,微環(huán)境的不允許。移植的神經(jīng)干細(xì)胞進(jìn)入體內(nèi)后,由于受到多種因素的影響,常保持未分化狀態(tài)或大部分分化為膠質(zhì)細(xì)胞。神經(jīng)干細(xì)胞向神經(jīng)元分化的調(diào)控機(jī)制及其影響因素直接決定神經(jīng)干細(xì)胞
2、源性神經(jīng)元的比例和神經(jīng)元Z間功能性突觸的數(shù)量?,F(xiàn)就其研究進(jìn)展做一綜述?!娟P(guān)鍵詞】神經(jīng)干細(xì)胞;神經(jīng)元;分化;調(diào)控機(jī)制;影響因素Abstract:Neuralstemcellsisakindofsplitpotentialandtheupdateabilitymothercells,itcanthroughthesymmetricaldivisionandasymmetricsplittingmethodsofgeneratingneuralorganizationofcells,includingneuro
3、ns,astrocytesandoligodcndrocytcs.Thecentralnervoussystemdamageneuronsandglia,afterthedamageresultedinclinicalsymptoms,endogenousneuralstemcellsrepaireffectisnotbig,thereasonisthenumberofstemcellsislimited,themicroenvironmentdonotal1owthis.Transplantedneur
4、alstemcells,afterentersthebodyduetotheinfluenceofmanyfactors,oftenkeepundifferentiatedstateormostdifferentiatedintoglialcells.Neuralstemcellstoneuronscontrolmechanismanditsinfluencingfactorsofneuralstemcellsinthesourcesexdirectlydeterminetheproportionofne
5、uronsbetweenneuronsandthenumberoffunctionalsynapses.Theresearchprogressisreviewedinthispaper.Keywords:Neuralstemcells;Neurons;Differentiation;Regulationmechanism;Influencefactors1神經(jīng)干細(xì)胞的來(lái)源:神經(jīng)干細(xì)胞(neuralstemcell,NSCs)可來(lái)源于神經(jīng)組織,也可來(lái)源于其他組織,如從哺乳動(dòng)物胚胎期的大部分腦區(qū)、成年期的腦室
6、下區(qū)、海馬齒狀冋的顆粒下層、脊髓等部位均成功分離出神經(jīng)干細(xì)胞;可由胚胎干細(xì)胞、胚胎生殖細(xì)胞等定向誘導(dǎo)分化而來(lái),也可來(lái)源于血液系統(tǒng)的骨髓間質(zhì)干細(xì)胞、成年多能祖細(xì)胞及臍血細(xì)胞等。其中SVZ(室管膜下區(qū))和SGZ(海馬齒狀回顆粒層)區(qū)已被證實(shí)是神經(jīng)前體細(xì)胞產(chǎn)生最為活躍的區(qū)域⑴叫2神經(jīng)干細(xì)胞向神經(jīng)元分化的過(guò)程:剛?cè)〔姆蛛x的神經(jīng)干細(xì)胞呈圓球狀,細(xì)胞比較飽滿,折光性強(qiáng)。繼續(xù)原代培養(yǎng)可見(jiàn)由多個(gè)神經(jīng)干細(xì)胞組成的細(xì)胞團(tuán),細(xì)胞團(tuán)呈不規(guī)則的圓形,大小不一致,細(xì)胞與細(xì)胞之間結(jié)合比較松散。繼之,神經(jīng)干細(xì)胞I才I變大,形態(tài)呈不規(guī)則狀
7、,細(xì)胞間結(jié)合較前緊密,邊緣清晰。繼續(xù)培養(yǎng),神經(jīng)球旁可見(jiàn)單離的細(xì)胞出現(xiàn),細(xì)胞胞體較小,周邊可見(jiàn)暈環(huán),并發(fā)出短小的突起,有的突起細(xì)長(zhǎng)類似軸突,有的有樹(shù)狀分支類似樹(shù)突,似多極或雙極類神經(jīng)元細(xì)胞。隨培養(yǎng)時(shí)間的延長(zhǎng),其細(xì)胞胞體增大,突起數(shù)量增多,長(zhǎng)度增長(zhǎng),細(xì)胞逐漸遠(yuǎn)離細(xì)胞球并分離。繼之多個(gè)細(xì)胞突起間建立細(xì)胞接觸,形成突觸樣結(jié)構(gòu)。3神經(jīng)干細(xì)胞向神經(jīng)元分化的影響因素及機(jī)制:神經(jīng)干細(xì)胞向神經(jīng)細(xì)胞分化的過(guò)程、神經(jīng)元占各種神經(jīng)細(xì)胞的比例及神經(jīng)元后期軸突和樹(shù)突的生長(zhǎng)等受到很多影響因子的影響。其中研究較多的包括:膜島素樣生長(zhǎng)因子
8、(IGF)、成纖維細(xì)胞生長(zhǎng)因子(FGF)、表皮生長(zhǎng)因子(EGF)、血管內(nèi)皮生長(zhǎng)因子(VEGF)、神經(jīng)營(yíng)養(yǎng)素3(NT?3)、腦源性神經(jīng)營(yíng)養(yǎng)因子(BDNF).肝細(xì)胞生長(zhǎng)因子(HGF)及三磷酸腺^(ATP))等。3.1膜島素樣生長(zhǎng)因了(insulin-likegrowthfactor,IGF)胰島素樣生長(zhǎng)因了家族有三種肽類生長(zhǎng)因子:朕島索(Tns)、IGF-I、IGF-II。其中TGF-1在神經(jīng)系統(tǒng)的發(fā)生發(fā)展屮起到重要的作用。胰島素