日前,，中科院遺傳與發(fā)育生物學(xué)研究所戴建武研究組成功利用三維培養(yǎng)，將皮膚細(xì)胞變成神經(jīng)干細(xì)胞,。相關(guān)研究成果發(fā)表于《生物材料》,。
2006年，山中伸彌利用逆轉(zhuǎn)錄病毒轉(zhuǎn)基因的方法實(shí)現(xiàn)體細(xì)胞重編程,，產(chǎn)生誘導(dǎo)性多能干細(xì)胞（iPS細(xì)胞）,，開創(chuàng)了基因調(diào)控細(xì)胞重編程的全新領(lǐng)域。隨后大量研究表明,，不同基因的聯(lián)合應(yīng)用可以誘導(dǎo)體細(xì)胞向多種類型細(xì)胞轉(zhuǎn)變,，如心肌細(xì)胞、神經(jīng)元細(xì)胞,、神經(jīng)干細(xì)胞,、血液祖細(xì)胞、胰島細(xì)胞等,。這些轉(zhuǎn)分化研究都是通過病毒轉(zhuǎn)染,、整合、基因過表達(dá)等手段調(diào)節(jié)細(xì)胞命運(yùn)的,，尋找更為安全的轉(zhuǎn)分化方法是重編程技術(shù)臨床應(yīng)用亟待解決的重要問題,。
三維細(xì)胞培養(yǎng)指在一定的環(huán)境條件下，將細(xì)胞種植在三維支架中,，構(gòu)建出具有特定形態(tài)和功能細(xì)胞的方法,。三維球狀形態(tài)（或者克隆形態(tài)）與干細(xì)胞特性密切相關(guān),，如胚胎干細(xì)胞在滋養(yǎng)層上以克隆形態(tài)生長，神經(jīng)干細(xì)胞以神經(jīng)球的形態(tài)生長,；克隆形成實(shí)驗(yàn)是鑒定干細(xì)胞的重要手段,，干細(xì)胞分化后失去克隆樣形態(tài),；多項研究也表明三維成球培養(yǎng)可以更好地維持干細(xì)胞的自我更新和多向分化特性,。然而，學(xué)界對于三維成球培養(yǎng)如何影響細(xì)胞重編程并不清楚,。
為此,，戴建武研究組對小鼠成纖維細(xì)胞進(jìn)行了三維成球培養(yǎng)，發(fā)現(xiàn)三維成球培養(yǎng)的小鼠成纖維細(xì)胞顯著上調(diào)了Sox2基因的表達(dá),，獲得了類似于神經(jīng)前體細(xì)胞的特性,，并具有分化為神經(jīng)元、星形膠質(zhì)細(xì)胞和少突膠質(zhì)細(xì)胞的能力,。當(dāng)其被注射到鼠大腦海馬部位后,，可以存活并在體內(nèi)分化為神經(jīng)元、星形膠質(zhì)細(xì)胞和少突膠質(zhì)細(xì)胞,。
業(yè)內(nèi)專家表示,，這些結(jié)果首次表明，不依賴基因,、RNA及蛋白的導(dǎo)入,，三維成球培養(yǎng)可以誘導(dǎo)成纖維細(xì)胞發(fā)生重編程，獲得神經(jīng)前體細(xì)胞特性,，為尋找更安全的轉(zhuǎn)分化方法提供了新思路,。
據(jù)悉，該項工作受到科技部重大科學(xué)研究計劃和中科院干細(xì)胞與再生醫(yī)學(xué)戰(zhàn)略先導(dǎo)科技專項資助,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Biomaterials DOI： 10.1016/j.biomaterials.2013.04.040
Direct conversion of fibroblasts into neural progenitor-like cells by forced growth into 3D spheres on low attachment surfaces
Guannan Sua, b, 1, Yannan Zhaoa, 1, Jianshu Weia, b, 1, Zhifeng Xiaoa, Bing Chena, Jin Hana, Lei Chena, b, Jian Guanc, Renzhi Wangc, Qun Dongd, Jianwu Daia
Many stem cells grow into three-dimensional (3D) spheres or colonies, such as neural progenitor cells (NPCs) and embryonic stem cells (ESCs). Sphere morphology helps maintaining the stemness of stem cells. Our previous study demonstrated that forced growth of RT4 and HEK293 cells into 3D sphere on low attachment surface could induce stem cell properties. The close relationship between 3D sphere morphology and stem cell stemness drives us to hypothesize that 3D sphere formation induces fibroblasts reprogramming. The key gene Sox2 for reprogramming fibroblasts into NPCs was found to be overexpressed in 3D sphere cultured mouse fibroblasts. These cells exhibited similar morphological and molecular features to NPCs in vitro, were capable of differentiating into neurons, astrocytes and oligodendrocytes, and could generate long-term expandable neurospheres while maintaining differentiation capability. When engrafted into hippocampus of adult rat brain, the 3D sphere cells differentiated into neural cells. Thus, NPCs can be generated from fibroblasts directly through a physical approach without introducing exogenous reprogramming factors.
