https://scholars.lib.ntu.edu.tw/handle/123456789/619713
標題: | Rho-associated kinase inhibitors promote the cardiac differentiation of embryonic and induced pluripotent stem cells | 作者: | Cheng, Ya-Ting Yeih, Dong-Feng Liang, Shu-Man Chien, Chia-Ying Yu, Yen-Ling BOR-SHENG KO Jan, Yee-Jee Kuo, Cheng-Chin Sung, Li-Ying Shyue, Song-Kun MING-FONG CHEN Yet, Shaw-Fang Wu, Kenneth K. Liou, Jun-Yang |
關鍵字: | Cardiac differentiation; Embryonic stem cells; Hematopoietic differentiation; Induced pluripotent stem cells; Rho-associated kinase | 公開日期: | 10-十月-2015 | 出版社: | Elsevier Ireland Ltd | 卷: | 201 | 起(迄)頁: | 441-448 | 來源出版物: | International Journal of Cardiology | 摘要: | Background Rho-associated kinase (ROCK) plays an important role in maintaining embryonic stem (ES) cell pluripotency. To determine whether ROCK is involved in ES cell differentiation into cardiac and hematopoietic lineages, we evaluated the effect of ROCK inhibitors, Y-27632 and fasudil on murine ES and induced pluripotent stem (iPS) cell differentiation. Methods Gene expression levels were determined by real-time PCR, Western blot analysis and immunofluorescent confocal microscopy. Cell transplantation of induced differentiated cells were assessed in vivo in a mouse model (three groups, n = 8/group) of acute myocardial infarction (MI). The cell engraftment was examined by immunohistochemical staining and the outcome was analyzed by echocardiography. Results Cells were cultured in hematopoietic differentiation medium in the presence or absence of ROCK inhibitor and colony formation as well as markers of ES, hematopoietic stem cells (HSC) and cells of cardiac lineages were analyzed. ROCK inhibition resulted in a drastic change in colony morphology accompanied by loss of hematopoietic markers (GATA-1, CD41 and β-Major) and expressed markers of cardiac lineages (GATA-4, Isl-1, Tbx-5, Tbx-20, MLC-2a, MLC-2v, α-MHC, cTnI and cTnT) in murine ES and iPS cells. Fasudil-induced cardiac progenitor (Mesp-1 expressing) cells were infused into a murine MI model. They engrafted into the peri-infarct and infarct regions and preserved left ventricular function. Conclusions These findings provide new insights into the signaling required for ES cell differentiation into hematopoietic as well as cardiac lineages and suggest that ROCK inhibitors are useful in directing iPS cell differentiation into cardiac progenitor cells for cell therapy of cardiovascular diseases. © 2015 Elsevier Ireland Ltd. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84943528174&doi=10.1016%2fj.ijcard.2015.08.118&partnerID=40&md5=6e32db5bf493274e5cf94ba8f18d062a https://scholars.lib.ntu.edu.tw/handle/123456789/619713 |
ISSN: | 0167-5273 | DOI: | 10.1016/j.ijcard.2015.08.118 |
顯示於: | 醫學系 |
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