PNAS：胚胎干細(xì)胞治療重要成果
來源：生物通
摘要：來自威斯康辛大學(xué)麥迪遜分校的研究人員發(fā)表了題為“Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network”的文章，證明了來源于胚胎干細(xì)胞人類的神經(jīng)元能夠調(diào)節(jié)宿主神經(jīng)細(xì)胞網(wǎng)絡(luò)行為，這朝著成功的神經(jīng)疾病細(xì)胞移植療法邁出的關(guān)鍵一步。相關(guān)成果 公布在《美國國家科學(xué)院院刊》
生物通報(bào)道：來自威斯康辛大學(xué)麥迪遜分校的研究人員發(fā)表了題為“Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network”的文章，證明了來源于胚胎干細(xì)胞人類的神經(jīng)元能夠調(diào)節(jié)宿主神經(jīng)細(xì)胞網(wǎng)絡(luò)行為，這朝著成功的神經(jīng)疾病細(xì)胞移植療法邁出的關(guān)鍵一步。相關(guān)成果 公布在《美國國家科學(xué)院院刊》（PNAS）雜志上。
以前已有研究證明，從干細(xì)胞中提取出的人類神經(jīng)元移植進(jìn)鼠大腦后，其能與鼠大腦中的主神經(jīng)元整合在一起并接收主神經(jīng)元發(fā)出的信號(hào)。但科學(xué)家們一直沒有證明這種移植細(xì)胞能成功地朝主神經(jīng)元發(fā)出信號(hào)并調(diào)控主神經(jīng)元的活動(dòng)。
在這篇文章中，研究人員將被光活化后的來自人類胚胎干細(xì)胞（hESCs）的神經(jīng)元移植有各種神經(jīng)性退化疾病的小鼠大腦，用于分析在體外及在小鼠大腦中的移植的人類細(xì)胞整合到小鼠神經(jīng)元的能力。
結(jié)果發(fā)現(xiàn)來自人類胚胎干細(xì)胞的神經(jīng)元可以在活小鼠的大腦中功能整合起，這可能對于研發(fā)針對帕金森病、阿茲海默病、中風(fēng)和癲癇的新治療方法具有重要意義，文章通訊作者Jason P. Weicka表示，這令人不可思議，現(xiàn)在從本質(zhì)上說, 我們能夠?yàn)樘囟ǖ募膊《ㄖ粕窠?jīng)元了。
研究人員把這些人類細(xì)胞與小鼠神經(jīng)元細(xì)胞共同培養(yǎng)，顯示出了同步的神經(jīng)活動(dòng)。 盡管來自人類胚胎干細(xì)胞的神經(jīng)元通常并不顯示出這種行為，這些人類細(xì)胞 逐漸在與小鼠神經(jīng)元的生長過程中出現(xiàn)了沖動(dòng)活動(dòng)。此外，用光刺激這些人類神經(jīng)元能引發(fā)小鼠神經(jīng)元的沖動(dòng)行為，這表明了人類與小鼠神經(jīng)元的互動(dòng)。光刺激也引 發(fā)了移植來自人類胚胎干細(xì)胞的神經(jīng)元的小鼠大腦切片的小鼠神經(jīng)元的響應(yīng)，這提示移植的神經(jīng)元可以通過功能整合參與到神經(jīng)元網(wǎng)絡(luò)并且控制神經(jīng)元網(wǎng)絡(luò)的活動(dòng)。
來自美國約翰霍普金斯大學(xué)的宋紅軍表示，“這十分令人激動(dòng)”，“你能夠放入小量的細(xì)胞并得到巨大的效果”，這項(xiàng)技術(shù)可提供一個(gè)平臺(tái)，讓科學(xué)家們研究諸如哪類主神經(jīng)元會(huì)做出反應(yīng)等問題。 研究人員現(xiàn)正在將這些光能激活的神經(jīng)元移植入罹患各種神經(jīng)退化性疾病的老鼠大腦中。
原文摘要：
Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network
Whether hESC-derived neurons can fully integrate with and functionally regulate an existing neural network remains unknown. Here, we demonstrate that hESC-derived neurons receive unitary postsynaptic currents both in vitro and in vivo and adopt the rhythmic firing behavior of mouse cortical networks via synaptic integration. Optical stimulation of hESC-derived neurons expressing Channelrhodopsin-2 elicited both inhibitory and excitatory postsynaptic currents and triggered network bursting in mouse neurons. Furthermore, light stimulation of hESC-derived neurons transplanted to the hippocampus of adult mice triggered postsynaptic currents in host pyramidal neurons in acute slice preparations. Thus, hESC-derived neurons can participate in and modulate neural network activity through functional synaptic integration, suggesting they are capable of contributing to neural network information processing both in vitro and in vivo.
Whether hESC-derived neurons can fully integrate with and functionally regulate an existing neural network remains unknown. Here, we demonstrate that hESC-derived neurons receive unitary postsynaptic currents both in vitro and in vivo and adopt the rhythmic firing behavior of mouse cortical networks via synaptic integration. Optical stimulation of hESC-derived neurons expressing Channelrhodopsin-2 elicited both inhibitory and excitatory postsynaptic currents and triggered network bursting in mouse neurons. Furthermore, light stimulation of hESC-derived neurons transplanted to the hippocampus of adult mice triggered postsynaptic currents in host pyramidal neurons in acute slice preparations. Thus, hESC-derived neurons can participate in and modulate neural network activity through functional synaptic integration, suggesting they are capable of contributing to neural network information processing both in vitro and in vivo.
