日本一個研究小組日前宣布,,他們開發(fā)出了利用誘導多能干細胞(iPS細胞)高效培養(yǎng)心肌細胞的方法,今后如果能夠利用這一方法大量培養(yǎng)心肌細胞,,將可用于恢復因心肌梗塞而受損的心臟功能,。
京都大學iPS細胞研究所副教授山下潤率領的研究小組,向?qū)嶒炇蟮膇PS細胞加入環(huán)孢菌素A(一種免疫抑制劑)后進行培養(yǎng),,發(fā)現(xiàn)發(fā)育成的心肌細胞數(shù)量是不加入環(huán)孢菌素A時的約12倍,。而利用人類iPS細胞進行培養(yǎng)時,在培養(yǎng)到第12天的時候,,確認生成的心肌細胞數(shù)量,,是不加入環(huán)孢菌素A時的4倍以上。
研究小組認為,,這表明環(huán)孢菌素A在誘導實驗鼠和人類iPS細胞發(fā)育成心肌細胞過程中發(fā)揮了重要作用,。
研究小組確認,利用人類iPS細胞培養(yǎng)的心肌細胞與人類心臟心室細胞擁有同樣的性質(zhì)和結構,。相關論文已刊登在新一期美國科學雜志《公共科學圖書館·綜合》網(wǎng)絡版上,。(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.