Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells

被引:36
作者
Yan, Peishi [1 ,2 ]
Nagasawa, Atsushi [2 ]
Uosaki, Hideki [1 ]
Sugimoto, Akihiro [2 ]
Yamamizu, Kohei [1 ]
Teranishi, Mizue [1 ]
Matsuda, Hiroyuki [3 ]
Matsuoka, Satoshi [3 ]
Ikeda, Tadashi [2 ]
Komeda, Masashi [4 ]
Sakata, Ryuzo [2 ]
Yamashita, Jun K. [1 ,5 ]
机构
[1] Kyoto Univ, Lab Stem Cell Differentiat, Stem Cell Res Ctr, Inst Frontier Med Sci,Sakyo Ku, Kyoto 6068507, Japan
[2] Kyoto Univ, Dept Cardiovasc Surg, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan
[3] Kyoto Univ, Dept Physiol & Biophys, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan
[4] Nagoya Heart Ctr, Nagoya, Aichi, Japan
[5] Kyoto Univ, Ctr iPS Cell Res & Applicat, Inst Integrated Cell Mat Sci, Sakyo Ku, Kyoto 6068507, Japan
关键词
Cyclosporin-A; Cardiac progenitor; Cardiomyocytes; Differentiation; Embryonic stem cells; SMOOTH-MUSCLE; TRANSCRIPTION FACTOR; NF-ATC; DIFFERENTIATION; IDENTIFICATION; CARDIOMYOCYTE; HEART;
D O I
10.1016/j.bbrc.2008.12.019
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Though cardiac progenitor cells should be a suitable material for cardiac regeneration, efficient ways to induce cardiac progenitors from embryonic stein (ES) cells have not been established. Extending our systematic cardiovascular differentiation method of ES cells, here we show efficient and specific expansion of cardiomyocytes and highly cardiogenic progenitors from ES cells. An immunosuppressant, cyclosporin A (CSA), showed a novel effect specifically acting on mesoderm cells to drastically increase cardiac progenitors as well as cardiomyocytes by 10-20 times. Approximately 200 cardiomyocytes could be induced from one mouse ES cell using this method. Expanded Progenitors Successfully integrated into scar tissue of infracted heart as cardiomyocytes after cell transplantation to rat myocardial infarction model. CSA elicited specific induction of cardiac lineage from mesoderm in a novel mesoderm-specific, NFAT independent fashion. This simple but efficient differentiation technology Would be extended to induce Pluripotent stein (iPS) cells and broadly contribute to cardiac regeneration. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:115 / 120
页数:6
相关论文
共 22 条
[1]   NFAT signaling: Choreographing the social lives of cells [J].
Crabtree, GR ;
Olson, EN .
CELL, 2002, 109 :S67-S79
[2]   Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum [J].
de la Pompa, JL ;
Timmerman, LA ;
Takimoto, H ;
Yoshida, H ;
Elia, AJ ;
Samper, E ;
Potter, J ;
Wakeham, A ;
Marengere, L ;
Langille, BL ;
Crabtree, GR ;
Mak, TW .
NATURE, 1998, 392 (6672) :182-186
[3]   A common progenitor at the heart of development [J].
Garry, Daniel J. ;
Olson, Eric N. .
CELL, 2006, 127 (06) :1101-1104
[4]   NFATc1 balances quiescence and proliferation of skin stem cells [J].
Horsley, Valerie ;
Aliprantis, Antonios O. ;
Polak, Lisa ;
Glimcher, Laurie H. ;
Fuchs, Elaine .
CELL, 2008, 132 (02) :299-310
[5]   Multipotent Flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages [J].
Kattman, Steven J. ;
Huber, Tara L. ;
Keller, Gordon M. .
DEVELOPMENTAL CELL, 2006, 11 (05) :723-732
[6]  
KODAMA H, 1994, EXP HEMATOL, V22, P979
[7]   Engraftment of engineered ES cell-derived cardiomyocytes but not BM cells restores contractile function to the infarcted myocardium [J].
Kolossov, Eugen ;
Bostani, Toktam ;
Roell, Wilhelm ;
Breitbach, Martin ;
Pillekamp, Frank ;
Nygren, Jens M. ;
Sasse, Philipp ;
Rubenchik, Olga ;
Fries, Jochen W. U. ;
Wenzel, Daniela ;
Geisen, Caroline ;
Xia, Ying ;
Lu, Zhongju ;
Duan, Yaqi ;
Kettenhofen, Ralf ;
Jovinge, Stefan ;
Bloch, Wilhelm ;
Bohlen, Heribert ;
Welz, Armin ;
Hescheler, Juergen ;
Jacobsen, Sten Eirik ;
Fleischmann, Bernd K. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (10) :2315-2327
[8]   Regenerating the heart [J].
Laflamme, MA ;
Murry, CE .
NATURE BIOTECHNOLOGY, 2005, 23 (07) :845-856
[9]   The potential of cardiac stem cell therapy for heart failure [J].
Lyon, Alexander ;
Harding, Sian .
CURRENT OPINION IN PHARMACOLOGY, 2007, 7 (02) :164-170
[10]   Multipotent embryonic Isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification [J].
Moretti, Alessandra ;
Caron, Leslie ;
Nakano, Atsushi ;
Lam, Jason T. ;
Bernshausen, Alexandra ;
Chen, Yinhong ;
Qyang, Yibing ;
Bu, Lei ;
Sasaki, Mika ;
Martin-Puig, Silvia ;
Sun, Yunfu ;
Evans, Sylvia M. ;
Laugwitz, Karl-Ludwig ;
Chien, Kenneth R. .
CELL, 2006, 127 (06) :1151-1165