Browse > Article

Effect of Extrinsic Factors on Differentiated Cardiomyocyte-like Cells from Human Embryonic Stem Cells  

Gil, Chang-Hyun (Graduate School of Life Science, CHA Stem Cell Institute, College of Medicine, CHA University)
Jang, Jae-Woo (Graduate School of Life Science, CHA Stem Cell Institute, College of Medicine, CHA University)
Lee, Won-Young (CHA Bio & Diostech Co., Ltd.)
Park, Ze-Won (Graduate School of Life Science, CHA Stem Cell Institute, College of Medicine, CHA University)
Lee, Jae-Ho (CHA Bio & Diostech Co., Ltd.)
Chung, Sun-Hwa (Graduate School of Life Science, CHA Stem Cell Institute, College of Medicine, CHA University)
Chae, Jung-Il (Graduate School of Life Science, CHA Stem Cell Institute, College of Medicine, CHA University)
Chung, Hyung-Min (Graduate School of Life Science, CHA Stem Cell Institute, College of Medicine, CHA University)
Publication Information
Reproductive and Developmental Biology / v.33, no.4, 2009 , pp. 263-271 More about this Journal
Abstract
Cardiovascular diseases (CVDs) are one of the most cause of death around the world and fields of interest for cardiac stem cells. Also, current use of terminally differentiated adult cardiomyocytes for CVDs has limited regenerative capacity therefore any significant cell loss may result in the development of progressive heart failure. Human embryonic stem cells (hESCs) derived from blastocyst-stage embryos spontaneously have ability to differentiate via embryo-like aggregates (endoderm, ectoderm and mesoderm) in vitro into various cell types including cardiomyocyte. However, most effective molecule or optimized condition which can induce cardiac differentiation of hESCs is rarely studied. In this study, we developed both spontaneous and inductive cardiomyocyte-like cells differentiation from hESCs by treatment of induced-factors, 5-azacytidine, BMP-4 and cardiogenol C. On the one hand, spontaneous and inductive cardiomyocyte-like cells showed that cardiac markers are expressed for further analysis by RT-PCR and immunocytochemistry. Interestingly, BMP-4 greatly improved homogeneous population of the cardiomyocyte-like cells from hESCs CHA15 and H09. In conclusion, we verified that spontaneously differentiated cells showed cardiac specific markers which characterize cardiac cells, treated extrinsic factors can manage cellular signals and found that hESCs can undergo differentiation into cardiomyocytes better than spontaneous group. This finding offers an insight into the inductive factor of differentiated cardiomyocytes and provides some helpful information that may offer the potential of cardiomyocytes derived from hESCs using extrinsic factors.
Keywords
hESC; Cardiomyocyte; Differentiation; BMP-4;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Ahn SE, Kim S, Park KH, Moon SH, Lee HJ, Kim GJ, Lee YJ, Park KH, Cha KY, Chung HM (2006): Primary bone-derived cells induce osteogenic differentiation without exogenous factors in human embryonic stem cells. Biochem Biophys Res Commun 340:403-408   DOI   ScienceOn
2 Cui L, Johkura, K, Takei, S, Ogiwara N, Sasaki K (2007): Structural differentiation, proliferation, and association of human embryonic stem cell-derived cardiomyocytes in vitro and in their extracardiac tissues. J Struct Biol 158:307-317   DOI   ScienceOn
3 Doss MX, Sachinidis A, Hescheler J (2008): Human ES cell derived cardiomyocytes for cell replacement therapy: a current update. Chin J Physiol 51:226- 229
4 He JQ, Ma Y, Lee Y, Thomson JA, Kamp TJ (2003): Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ Res 93:32-39   DOI   ScienceOn
5 Pawlak A, Gil RJ (2007): Desmin--an important structural protein of a cardiac myocyte. Kardiol Pol 65:303-309   ScienceOn
6 Schuh A, Breuer S, Al Dashti R, Sulemanjee N, Han rath P, Weber C, Uretsky BF, Schwarz ER (2005): Administration of vascular endothelial growth factor adjunctive to fetal cardiomyocyte transplantation and improvement of cardiac function in the rat model. J Cardiovasc Pharmacol Ther 10:55-66   DOI   ScienceOn
7 aylor SM, Jones PA (1979): Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell 17:771-779   DOI   ScienceOn
8 Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998): Embryonic stem cell lines derived from human blastocysts. Science 282:1145-1147   DOI   ScienceOn
9 Van den Brule FA, Fernandez PL, Buicu C, Liu FT, Jackers P, Lambotte R, Castronovo V (1997): Differential expression of galectin-1 and galectin-3 during first trimester human embryogenesis. Dev Dyn 209:399-405   DOI   ScienceOn
10 El-Bizri N, Guignabert C, Wang L, Cheng A, Stankunas K, Chang CP, Mishina Y, Rabinovitch M (2008): SM22 alpha-targeted deletion of bone morphogenetic protein receptor 1A in mice impairs cardiac and vascular development, and influences organogenesis. Development 135:2981-2991   DOI   ScienceOn
11 Gepstein L (2008): Experimental molecular and stem cell therapies in cardiac electrophysiology. Ann N Y Acad Sci 1123:224-231   DOI   ScienceOn
12 Kehat I, Gepstein L (2003): Human embryonic stem cells for myocardial regeneration. Heart Fail Rev 8:229-236   DOI   ScienceOn
13 Gerecht-Nir SG, Itskovitz-Eldor J (2004): Human embryonic stem cells: a potential source for cellular therapy. Am J Transplant 4:51-57   DOI
14 Kehat I, Khimovich L, Caspi O, Gepstein A, Shofti R, Arbel G, Huber I, Satin J, Itskovitz-Eldor J, Gepstein L (2004): Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nat Biotechnol 22:1282-1289   DOI   ScienceOn
15 Taylor DA, Atkins BZ, Hungspreugs P, Jones TR, Reedy MC, Hutcheson KA, Glower DD, Kraus WE (1998): Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 4:929-933   DOI   ScienceOn
16 Doll D, Sarikas A, Krajcik R, Zolk O (2007): Proteomic expression analysis of cardiomyocytes subjected to proteasome inhibition. Biochem Biophys Res Commun 353:436-442   DOI   ScienceOn
17 Schlange T, Andree B, Arnold HH, Brand T (2000): BMP2 is required for early heart development during a distinct time period. Mech Dev 91:259-270   DOI   ScienceOn
18 Bruce SJ, Gardiner BB, Burke LJ, Gongora MM, Grimmond SM, Perkins AC (2007): Dynamic transcription programs during ES cell differentiation towards mesoderm in serum versus serum-free BMP4 culture. BMC Genomics 8:365   DOI
19 Gerecht-Nir SG, David R, Zaruba M, Franz WM, Itskovitz-Eldor J (2003): Human embryonic stem cells for cardiovascular repair. Cardiovasc Res 58:313- 323   DOI   ScienceOn
20 Li RK, Mickle DA, Weisel RD, Mohabeer MK, Zhang J, Rao V, Li G, Merante F, Jia ZQ (1997): Natural history of fetal rat cardiomyocytes transplanted into adult rat myocardial scar tissue. Circulation 96:II-179-86; discussion 186-187
21 Boheler KR, Czyz J, Tweedie D, Yang HT, Anisimov SV, Wobus AM (2002): Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res 91:189-201   DOI   ScienceOn
22 Tran TH, Wang X, Browne C, Zhang Y, Schinke M, Izumo S, Burcin M (2009): Wnt3a-induced mesoderm formation and cardiomyogenesis in human embryonic stem cells. Stem Cells 27:1869-1878   DOI   ScienceOn
23 Murry CE, Keller G (2008): Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell 132:661- 680   DOI   ScienceOn
24 Xu C, Police S, Rao N, Carpenter MK (2002): Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res 91:501-508   DOI   ScienceOn
25 Spradling A, Drummond-Barbosa D, Kai T (2001): Stem cells find their niche. Nature 414:98-104   DOI   ScienceOn
26 Ge D, Liu X, Li L, Wu J, Tu Q, Shi Y, Chen H (2009): Chemical and physical stimuli induce cardiomyocyte differentiation from stem cells. Biochem Biophys Res Commun 381:317-321   DOI   ScienceOn
27 Goumans MJ, de Boer TP, Smits AM, van Laake LW, van Vliet P, Metz CH, Korfage TH, Kats KP, Hochstenbach R, Pasterkamp G, Verhaar MC, van der Heyden MA, de Kleijn D, Mummery CL, van Veen TA, Sluijter JP, Doevendans PA (2007): TGF- beta1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro. Stem Cell Res 1:138-149   DOI   ScienceOn
28 Evans MJ, Kaufman MH (1981): Establishment in culture of pluripotential cells from mouse embryos. Nature 292:154-296   DOI   ScienceOn
29 Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001): Bone marrow cells regenerate infarcted myocardium. Nature 410:701-705   DOI   ScienceOn
30 Passier R, Oostwaard DW, Snapper J, Kloots J, Hassink RJ, Kuijk E, Roelen B, de la Riviere AB, Mummery C (2005): Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures. Stem Cells 23:772-780   DOI   ScienceOn
31 Solter D, Shevinsky L, Knowles BB, Strickland S (1979): The induction of antigenic changes in a teratocarcinoma stem cell line (F9) by retinoic acid. Dev Biol 70:515-521   DOI   ScienceOn
32 Goldmann WH (2000): Binding of tropomyosin-troponin to actin increases filament bending stiffness. Biochem Biophys Res Commun 276:1225-1228   DOI   ScienceOn
33 Pease S, Braghetta P, Gearing D, Grail D, Williams RL (1990): Isolation of embryonic stem (ES) cells in media supplemented with recombinant leukemia inhibitory factor (LIF). Dev Biol 141:344-352   DOI   ScienceOn
34 Taylor SM, Jones PA (1982): Changes in phenotypic expression in embryonic and adult cells treated with 5-azacytidine. J Cell Physiol 111:187- 194   DOI
35 Beqqali A, van Eldik W, Mummery C, Passier R (2009): Human stem cells as a model for cardiac differentiation and disease. Cell Mol Life Sci 66:800- 813   DOI   ScienceOn
36 Lazarides E (1980): Intermediate filaments as mechanical integrators of cellular space. Nature 283:249- 256   DOI   ScienceOn
37 Goldman BI, Wurzel J (1992): Effects of subcultivation and culture medium on differentiation of human fetal cardiac myocytes. In Vitro Cell Dev Biol 28A:109-119   DOI
38 Jones PA, Taylor SM (1980): Cellular differentiation, cytidine analogs and DNA methylation. Cell 20: 85-93   DOI   ScienceOn
39 Freund C, Mummery CL (2009): Prospects for pluripotent stem cell-derived cardiomyocytes in cardiac cell therapy and as disease models. J Cell Biochem 107:592-599   DOI   ScienceOn
40 Gai H, Leung EL, Costantino PD, Aguila JR, Nguyen DM, Fink LM, Ward DC, Ma Y (2009): Generation and characterization of functional cardiomyocytes using induced pluripotent stem cells derived from human fibroblasts. Cell Biol Int 33:1184-1193   DOI   ScienceOn
41 Takei S, Ichikawa H, Johkura K, Mogi A, No H, Yoshie S, Tomotsune D, Sasaki K. (2009): Bone morphogenetic protein-4 promotes induction of cardiomyocytes from human embryonic stem cells in serum-based embryoid body development. Am J Physiol Heart Circ Physiol 296: H1793-803   DOI   ScienceOn
42 Mummery C, Ward D, van den Brink CE, Bird SD, Doevendans PA, Opthof T, Brutel de la Riviere A, Tertoolen L, van der Heyden M, Pera M (2002): Cardiomyocyte differentiation of mouse and human embryonic stem cells. J Anat 200:233-242   DOI   ScienceOn
43 Monzen K, Shiojima I, Hiroi Y, Kudoh S, Oka T, Takimoto E, Hayashi D, Hosoda T, Habara-Ohkubo A, Nakaoka T, Fujita T, Yazaki Y, Komuro I (1999): Bone morphogenetic proteins induce cardiomyocyte differentiation through the mitogen-activated protein kinase kinase kinase TAK1 and cardiac transcription factors Csx/Nkx-2.5 and GATA-4. Mol Cell Biol 19:7096-7105   ScienceOn
44 Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M, Gepstein A, Livne E, Binah O, Itskovitz-Eldor J, Gepstein L (2001): Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 108: 407-414   DOI
45 Pal R, Khanna A (2007): Similar pattern in cardiac differentiation of human embryonic stem cell lines, BG01V and ReliCellhES1, under low serum concentration supplemented with bone morphogenetic protein-2. Differentiation 75:112-122   DOI   ScienceOn
46 Parkes JG, Liu Y, Sirna JB, Templeton DM (2000): Changes in gene expression with iron loading and chelation in cardiac myocytes and non-myocytic fibroblasts. J Mol Cell Cardiol 32:233-246   DOI   ScienceOn
47 Wu X, Ding S, Ding Q, Gray NS, Schultz PG (2004): Small molecules that induce cardiomyogenesis in embryonic stem cells. J Am Chem Soc 126:1590- 1591   DOI   ScienceOn
48 Lehman W, Hatch V, Korman V, Rosol M, Thomas L, Maytum R, Geeves MA, Van Eyk JE, Tobacman LS, Craig R (2000): Tropomyosin and actin isoforms modulate the localization of tropomyosin strands on actin filaments. J Mol Biol 302:593-606   DOI   ScienceOn
49 Yoon BS, Yoo SJ, Lee JE, You S, Lee HT, Yoon HS (2006): Enhanced differentiation of human embryonic stem cells into cardiomyocytes by combining hanging drop culture and 5-azacytidine treatment. Differentiation 74:149-159   DOI   ScienceOn
50 Lepore JJ, Cheng L, Min Lu M, Mericko PA, Morrisey EE, Parmacek MS (2005): High-efficiency somatic mutagenesis in smooth muscle cells and cardiac myocytes in SM22alpha-Cre transgenic mice. Genesis 41:179-184   DOI   ScienceOn
51 Passier R, Mummery C (2005): Cardiomyocyte differentiation from embryonic and adult stem cells. Curr Opin Biotechnol 16:498-502   DOI   ScienceOn
52 Monzen K, Hiroi Y, Kudoh S, Akazawa H, Oka T, Takimoto E, Hayashi D, Hosoda T, Kawabata M, Miyazono K, Ishii S, Yazaki Y, Nagai R, Komuro I (2001): Smads, TAK1, and their common target ATF- 2 play a critical role in cardiomyocyte differentiation. J Cell Biol 153:687-698   DOI   ScienceOn
53 tskovitz-Eldor J, Schuldiner M, Karsenti D, Eden A, Yanuka O, Amit M, Soreq H, Benvenisty N (2000): Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med 6:88-95   ScienceOn