日本東京大學(xué)的研究人員宣布,他們開發(fā)出了用誘導(dǎo)多能干細(xì)胞(iPS細(xì)胞)制造血小板的技術(shù),并通過動物實驗確認(rèn)了制造出來的血小板具有止血功能,。
iPS細(xì)胞是具有較強分化潛力的干細(xì)胞,由皮膚細(xì)胞等體細(xì)胞經(jīng)基因改造“誘導(dǎo)”發(fā)育而成。培養(yǎng)這類細(xì)胞不需要利用人類早期胚胎,而且可以無限增殖,,因此新技術(shù)有望用于大量生產(chǎn)輸血用的血小板。
東京大學(xué)副教授江藤浩之率領(lǐng)的研究小組,,在22日的美國《實驗醫(yī)學(xué)雜志》月刊上發(fā)表論文說,,他們首先利用人體皮膚纖維組織母細(xì)胞和臍帶血細(xì)胞制造出iPS細(xì)胞,然后加入幾種血液細(xì)胞增殖因子和營養(yǎng)細(xì)胞,,培養(yǎng)出能夠制造血小板的巨核細(xì)胞,,最終制造出血小板。
研究人員將制造出的血小板輸給小鼠,,發(fā)現(xiàn)血小板集中到受傷的血管上,,形成血栓,正常發(fā)揮了血小板的功能,。
研究人員使用了與癌癥有關(guān)的cMyc基因,,能夠高效制造巨核細(xì)胞并生產(chǎn)血小板。由于血小板中不存在含有遺傳信息的細(xì)胞核,,而且混雜其中的其他細(xì)胞的細(xì)胞核可以通過照射放射線和過濾去除,,所以臨床應(yīng)用時不會有癌變的危險。
血小板是血液細(xì)胞之一,,能夠凝固血液,,防止出血。手術(shù)時使用的血小板現(xiàn)在完全依賴獻血,。研究小組準(zhǔn)備確認(rèn)新技術(shù)的安全性之后,,早日將其應(yīng)用于手術(shù)。(生物谷Bioon.com)
生物谷推薦英文摘要:
JEM doi: 10.1084/jem.20100844
Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells
Naoya Takayama1, Satoshi Nishimura3,4,5, Sou Nakamura1, Takafumi Shimizu2, Ryoko Ohnishi1, Hiroshi Endo1,2, Tomoyuki Yamaguchi2, Makoto Otsu2, Ken Nishimura4,6, Mahito Nakanishi6, Akira Sawaguchi7, Ryozo Nagai3,5, Kazutoshi Takahashi8, Shinya Yamanaka8, Hiromitsu Nakauchi2, and Koji Eto1
1Stem Cell Bank and 2Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, the Institute of Medical Science, and 3Department of Cardiovascular Medicine and 5Translational Systems Biology and Medicine Initiative, the University of Tokyo, Tokyo 113-0033, Japan
4PRESTO, Japan Science and Technology Agency, Tokyo 102-8666, Japan
6Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, Ibaraki 305–8562, Japan
7Department of Anatomy, University of Miyazaki Faculty of Medicine, Miyazaki 889-1692, Japan
8Center for iPS Research and Application, Kyoto University, Kyoto 606-8507, Japan
Human (h) induced pluripotent stem cells (iPSCs) are a potentially abundant source of blood cells, but how best to select iPSC clones suitable for this purpose from among the many clones that can be simultaneously established from an identical source is not clear. Using an in vitro culture system yielding a hematopoietic niche that concentrates hematopoietic progenitors, we show that the pattern of c-MYC reactivation after reprogramming influences platelet generation from hiPSCs. During differentiation, reduction of c-MYC expression after initial reactivation of c-MYC expression in selected hiPSC clones was associated with more efficient in vitro generation of CD41a+CD42b+ platelets. This effect was recapitulated in virus integration-free hiPSCs using a doxycycline-controlled c-MYC expression vector. In vivo imaging revealed that these CD42b+ platelets were present in thrombi after laser-induced vessel wall injury. In contrast, sustained and excessive c-MYC expression in megakaryocytes was accompanied by increased p14 (ARF) and p16 (INK4A) expression, decreased GATA1 expression, and impaired production of functional platelets. These findings suggest that the pattern of c-MYC expression, particularly its later decline, is key to producing functional platelets from selected iPSC clones.