日本一個(gè)研究小組日前宣布,他們開(kāi)發(fā)出了利用誘導(dǎo)多能干細(xì)胞(iPS細(xì)胞)高效培養(yǎng)心肌細(xì)胞的方法,,今后如果能夠利用這一方法大量培養(yǎng)心肌細(xì)胞,,將可用于恢復(fù)因心肌梗塞而受損的心臟功能。
京都大學(xué)iPS細(xì)胞研究所副教授山下潤(rùn)率領(lǐng)的研究小組,,向?qū)嶒?yàn)鼠的iPS細(xì)胞加入環(huán)孢菌素A(一種免疫抑制劑)后進(jìn)行培養(yǎng),,發(fā)現(xiàn)發(fā)育成的心肌細(xì)胞數(shù)量是不加入環(huán)孢菌素A時(shí)的約12倍。而利用人類iPS細(xì)胞進(jìn)行培養(yǎng)時(shí),,在培養(yǎng)到第12天的時(shí)候,,確認(rèn)生成的心肌細(xì)胞數(shù)量,是不加入環(huán)孢菌素A時(shí)的4倍以上,。
研究小組認(rèn)為,,這表明環(huán)孢菌素A在誘導(dǎo)實(shí)驗(yàn)鼠和人類iPS細(xì)胞發(fā)育成心肌細(xì)胞過(guò)程中發(fā)揮了重要作用。
研究小組確認(rèn),,利用人類iPS細(xì)胞培養(yǎng)的心肌細(xì)胞與人類心臟心室細(xì)胞擁有同樣的性質(zhì)和結(jié)構(gòu),。相關(guān)論文已刊登在新一期美國(guó)科學(xué)雜志《公共科學(xué)圖書館·綜合》網(wǎng)絡(luò)版上,。(生物谷Bioon.com)
生物谷推薦原文出處:
PLoS ONE 6(2): e16734. doi:10.1371/journal.pone.0016734
Induction and Enhancement of Cardiac Cell Differentiation from Mouse and Human Induced Pluripotent Stem Cells with Cyclosporin-A
Masataka Fujiwara1,2, Peishi Yan1,3¤, Tomomi G. Otsuji4,5, Genta Narazaki1,6, Hideki Uosaki1,6, Hiroyuki Fukushima1,6, Koichiro Kuwahara2, Masaki Harada2, Hiroyuki Matsuda7, Satoshi Matsuoka7, Keisuke Okita8, Kazutoshi Takahashi8, Masato Nakagawa8, Tadashi Ikeda3, Ryuzo Sakata3, Christine L. Mummery9, Norio Nakatsuji10,11, Shinya Yamanaka8,12, Kazuwa Nakao2, Jun K. Yamashita1,6*
Induced pluripotent stem cells (iPSCs) are novel stem cells derived from adult mouse and human tissues by reprogramming. Elucidation of mechanisms and exploration of efficient methods for their differentiation to functional cardiomyocytes are essential for developing cardiac cell models and future regenerative therapies. We previously established a novel mouse embryonic stem cell (ESC) and iPSC differentiation system in which cardiovascular cells can be systematically induced from Flk1+ common progenitor cells, and identified highly cardiogenic progenitors as Flk1+/CXCR4+/VE-cadherin? (FCV) cells. We have also reported that cyclosporin-A (CSA) drastically increases FCV progenitor and cardiomyocyte induction from mouse ESCs. Here, we combined these technologies and extended them to mouse and human iPSCs. Co-culture of purified mouse iPSC-derived Flk1+ cells with OP9 stroma cells induced cardiomyocyte differentiation whilst addition of CSA to Flk1+ cells dramatically increased both cardiomyocyte and FCV progenitor cell differentiation. Spontaneously beating colonies were obtained from human iPSCs by co-culture with END-2 visceral endoderm-like cells. Appearance of beating colonies from human iPSCs was increased approximately 4.3 times by addition of CSA at mesoderm stage. CSA-expanded human iPSC-derived cardiomyocytes showed various cardiac marker expressions, synchronized calcium transients, cardiomyocyte-like action potentials, pharmacological reactions, and ultra-structural features as cardiomyocytes. These results provide a technological basis to obtain functional cardiomyocytes from iPSCs.