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盡管干細(xì)胞被廣泛地用來測試新藥,,但是研究人員總是很難在體外生產(chǎn)足夠多的有活性的干細(xì)胞,。通常干細(xì)胞是在必須經(jīng)過刮擦的平面上培養(yǎng)的,然后它們必須分化為其他細(xì)胞類型以便阻止這些非常重要的細(xì)胞死亡,。經(jīng)證實(shí),,這是一種沒有效率的收集干細(xì)胞的方法,因?yàn)檫@種過程不能產(chǎn)生足夠多數(shù)量的干細(xì)胞,,而且所需成本較高,。
為了解決這種問題,來自加拿大多倫多大學(xué)生物材料與生物醫(yī)學(xué)工程研究所的博士后研究員David Fluri和教授Peter Zandstra決定將被稱作重編程的干細(xì)胞產(chǎn)生過程與生物反應(yīng)器使用結(jié)合起來,,其中生物反應(yīng)器提供穩(wěn)定的環(huán)境條件,。通過這種過程,F(xiàn)luri能夠?qū)⑿∈蠹?xì)胞重編程為多能性干細(xì)胞,,然后將誘導(dǎo)它們分化為心肌細(xì)胞,。
通過將干細(xì)胞培養(yǎng)物放置在特定的生物反應(yīng)器中,這些干細(xì)胞就進(jìn)行懸浮培養(yǎng),,從而消除在表面培養(yǎng)它們時(shí)存在的內(nèi)在問題,。
由于這項(xiàng)發(fā)現(xiàn)更加適合于干細(xì)胞大規(guī)模生產(chǎn)過程,F(xiàn)luri希望它應(yīng)當(dāng)有助于緩解干細(xì)胞生產(chǎn)的瓶頸問題,,從而有助于這些干細(xì)胞用于研究和藥物開發(fā),。
不過,F(xiàn)luri的發(fā)現(xiàn)帶來的影響還包括:一旦產(chǎn)生干細(xì)胞,,它們就很容易分化為其他類型的細(xì)胞如心肌細(xì)胞,,但是Fluri的新培養(yǎng)過程有潛力使得這種干細(xì)胞生產(chǎn)過程更加安全和更加穩(wěn)定,。
相關(guān)研究結(jié)果于2012年3月25日在線發(fā)表在Nature Methods期刊上(生物谷:towersimper編譯)
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doi:10.1038/nmeth.1939
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Derivation, expansion and differentiation of induced pluripotent stem cells in continuous suspension cultures
David A Fluri, Peter D Tonge, Hannah Song, Ricardo P Baptista, Nika Shakiba, Shreya Shukla, Geoffrey Clarke, Andras Nagy & Peter W Zandstra
We describe derivation of induced pluripotent stem cells (iPSCs) from terminally differentiated mouse cells in serum- and feeder-free stirred suspension cultures. Temporal analysis of global gene expression revealed high correlations between cells reprogrammed in suspension and cells reprogrammed in adhesion-dependent conditions. Suspension culture–reprogrammed iPSCs (SiPSCs) could be differentiated into all three germ layers in vitro and contributed to chimeric embryos in vivo. SiPSC generation allowed for efficient selection of reprogramming factor–expressing cells based on their differential survival and proliferation in suspension culture. Seamless integration of SiPSC reprogramming and directed differentiation enabled scalable production of beating cardiac cells in a continuous single cell– and small aggregate–based process. This method is an important step toward the development of robust PSC generation, expansion and differentiation technology.