關(guān)鍵詞： 間充質(zhì)干細(xì)胞 MSC 胚胎干細(xì)胞 誘導(dǎo)性多功能干細(xì)胞 骨髓 成體干細(xì)胞
澳大利亞昆士蘭大學(xué)科學(xué)家在世界上首次開發(fā)出生產(chǎn)成體干細(xì)胞的方法,，這一研究成果將深刻影響著患有一系列嚴(yán)重性疾病的病人,。
這項(xiàng)研究是包括昆士蘭大學(xué)澳大利亞生物工程和納米技術(shù)研究所在內(nèi)的多家研究機(jī)構(gòu)合作開展的，由昆士蘭大學(xué)臨床研究中心教授Nicholas Fisk領(lǐng)導(dǎo),。
間充質(zhì)干細(xì)胞(mesenchymal stem cells, MSCs)能夠被用來修復(fù)骨骼和潛在性地修復(fù)其他器官,。這項(xiàng)研究揭示一種生產(chǎn)間充質(zhì)干細(xì)胞的新方法,。
Fisk教授說，“我們使用一種小分子SB431542---一種轉(zhuǎn)化生長因子β (transforming growth factor-β, TGF-β)途徑抑制劑---誘導(dǎo)胚胎干細(xì)胞10天(就可產(chǎn)生間充質(zhì)干細(xì)胞),，產(chǎn)生速度要比文獻(xiàn)中報(bào)道的其他研究快得多,。這種技術(shù)也可適用于較少引起爭議的誘導(dǎo)性多功能干細(xì)胞(induced pluripotent stem cell, iPSC)。”
“為了使得多能性成熟干細(xì)胞能夠應(yīng)用于臨床，在注射到受損器官之前,，它們必須收到告訴它們需要變成哪些細(xì)胞類型的信號,，否則它們可能形成腫瘤。”
“因?yàn)橹挥猩倭块g充質(zhì)干細(xì)胞存在于骨髓中而且從健康供者中收集骨髓的方法是侵入式的,，所以在實(shí)驗(yàn)室中能夠大量制造我們自己的間充質(zhì)干細(xì)胞是未來間充質(zhì)干細(xì)胞大規(guī)模用于臨床治療的一次激動(dòng)人心的進(jìn)步,。”
“我們能夠證實(shí)這些新形式的干細(xì)胞表現(xiàn)出骨髓干細(xì)胞的所有特征，而且我們當(dāng)前正在研究它們的骨修復(fù)能力,。”
澳大利亞生物工程和納米技術(shù)研究所副教授和該研究項(xiàng)目的共同研究員Ernst Wolvetang說,，就基于干細(xì)胞的療法的醫(yī)學(xué)轉(zhuǎn)化而言，這種新方法已克服了一道重要的障礙,。
Wolvetang副教授說,，“我們對這項(xiàng)研究感到非常激動(dòng)。”
這項(xiàng)研究成果發(fā)表在2012年2月份那期《干細(xì)胞轉(zhuǎn)化醫(yī)學(xué)》期刊上,。(生物谷：towersimper編譯)
doi:10.5966/sctm.2011-0022
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Small Molecule Mesengenic Induction of Human Induced Pluripotent Stem Cells to Generate Mesenchymal Stem/Stromal Cells
Yen Shun Chen, Rebecca A. Pelekanos, Rebecca L. Ellis, Rachel Horne, Ernst J. Wolvetang and Nicholas M. Fisk
The translational potential of mesenchymal stem/stromal cells (MSCs) is limited by their rarity in somatic organs, heterogeneity, and need for harvest by invasive procedures. Induced pluripotent stem cells (iPSCs) could be an advantageous source of MSCs, but attempts to derive MSCs from pluripotent cells have required cumbersome or untranslatable techniques, such as coculture, physical manipulation, sorting, or viral transduction. We devised a single-step method to direct mesengenic differentiation of human embryonic stem cells (ESCs) and iPSCs using a small molecule inhibitor. First, epithelial-like monolayer cells were generated by culturing ESCs/iPSCs in serum-free medium containing the transforming growth factor-β pathway inhibitor SB431542. After 10 days, iPSCs showed upregulation of mesodermal genes (MSX2, NCAM, HOXA2) and downregulation of pluripotency genes (OCT4, LEFTY1/2). Differentiation was then completed by transferring cells into conventional MSC medium. The resultant development of MSC-like morphology was associated with increased expression of genes, reflecting epithelial-to-mesenchymal transition. Both ESC- and iPSC-derived MSCs exhibited a typical MSC immunophenotype, expressed high levels of vimentin and N-cadherin, and lacked expression of pluripotency markers at the protein level. Robust osteogenic and chondrogenic differentiation was induced in vitro in ES-MSCs and iPS-MSCs, whereas adipogenic differentiation was limited, as reported for primitive fetal MSCs and ES-MSCs derived by other methods. We conclude that treatment with SB431542 in two-dimensional cultures followed by culture-induced epithelial-to-mesenchymal transition leads to rapid and uniform MSC conversion of human pluripotent cells without the need for embryoid body formation or feeder cell coculture, providing a robust, clinically applicable, and efficient system for generating MSCs from human iPSCs.
