澳大利亞昆士蘭大學科學家在世界上首次開發出生產成體幹細胞的方法,這一研究成果將深刻影響著患有一系列嚴重性疾病的病人。
這項研究是包括昆士蘭大學澳大利亞生物工程和納米技術研究所在內的多家研究機構合作開展的,由昆士蘭大學臨床研究中心教授Nicholas Fisk領導。
間充質幹細胞(mesenchymal stem cells, MSCs)能夠被用來修復骨骼和潛在性地修復其他器官。這項研究揭示一種生產間充質幹細胞的新方法。
Fisk教授說,「我們使用一種小分子SB431542---一種轉化生長因子β (transforming growth factor-β, TGF-β)途徑抑制劑---誘導胚胎幹細胞10天(就可產生間充質幹細胞),產生速度要比文獻中報導的其他研究快得多。這種技術也可適用於較少引起爭議的誘導性多功能幹細胞(induced pluripotent stem cell, iPSC)。」
「為了使得多能性成熟幹細胞能夠應用於臨床,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胞類型的信號,否則它們可能形成腫瘤。」
「因為只有少量間充質幹細胞存在於骨髓中而且從健康供者中收集骨髓的方法是侵入式的,所以在實驗室中能夠大量製造我們自己的間充質幹細胞是未來間充質幹細胞大規模用於臨床治療的一次激動人心的進步。」
「我們能夠證實這些新形式的幹細胞表現出骨髓幹細胞的所有特徵,而且我們當前正在研究它們的骨修復能力。」
澳大利亞生物工程和納米技術研究所副教授和該研究項目的共同研究員Ernst Wolvetang說,就基於幹細胞的療法的醫學轉化而言,這種新方法已克服了一道重要的障礙。
Wolvetang副教授說,「我們對這項研究感到非常激動。」
這項研究成果發表在2012年2月份那期《幹細胞轉化醫學》期刊上。(生物谷:towersimper編譯)
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.