Experimental Research of Small Molecule Compound XAV939 Inducing Mouse Embryonic Stem Cell into Cardiac Myocyte_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

XUShi-jun ,  MUJun-sheng , ZHANGJian-qun , BOPing

Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, P. R. China;

Corresponding author：

MUJun-sheng, Email: wesleymu@hotmail.com

Keywords：

Mouse embryonic stem cells; Cardiac myocyte; XAV939; Cell differentiation

DOI：

10.7507/1007-4848.20160171

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the feasibility of small molecule compound XAV939 to induce mouse embryonic stem cells (mESC) to differentiate into cardiac myocytes. Methods We revived and cultured undifferentiated mESC growing confluently on trophoderm made of mouse embryonic inoblast cell. The mESCs were digested by trypsin to form embryoid bodies (EBs) by handing drop method. After plated, EBs were induced by XAV939 to differentiate into cardiac myocytes. We observed the cardiac myocytes with lightmicroscopy and identified it with immunofluorescence method. Result The XAV939 can effectively induce mESC into cardiac myocytes with the mean efficiency rate of 71.85%±1.05%. The differentiated cardiac myocytes shrinked spanteously and rhythmicly. The cardiac troponin T as the special marker of cardiac myocyte was positive. Conclusion The small molecule compound XAV939 could effectively induce mES cells into cardiac myocytes.

Citation： XUShi-jun, MUJun-sheng, ZHANGJian-qun, BOPing. Experimental Research of Small Molecule Compound XAV939 Inducing Mouse Embryonic Stem Cell into Cardiac Myocyte. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2016, 23(7): 714-718. doi: 10.7507/1007-4848.20160171 Copy

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7.	Fu JD, Srivastava D. Direct reprogramming of fibroblasts into cardiomyocytes for cardiac regenerative medicine. Circ J, 2015, 79(2):245-254.
8.	Boheler KR, Czyz J, Tweedie D, et al. Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res, 2002, 91(3):189-201.
9.	Jasmin D, Spray C, Campos DC, et al. Chemical induction of cardiac differentiation in p19 embryonal carcinoma stem cells. Stem Cells Dev, 2010, 19(3):403-412.
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13.	Moon RT, Kohn AD, De Ferrari GV, et al. WNT and beta-catenin signalling:diseases and therapies. Nat Rev Genet, 2004, 5(9):691-701.
14.	Kuhl M, Geis K, Sheldahl LC, et al. Antagonistic regulation of convergent extension movements in Xenopus by Wnt/beta-catenin and Wnt/Ca2+ signaling. Mech Dev, 2001, 106(1-2):61-76.
15.	Maye P, Zheng J, Li L, et al. Multiple mechanisms for Wnt11-mediated repression of the canonical Wnt signaling pathway. J Biol Chem, 2004, 279(23):24659-24665.
16.	Eisenberg LM, Eisenberg CA. Wnt signal transduction and the formation of the myocardium. Dev Biol, 2006, 293(2):305-315.
17.	Nakamura T, Sano M, Song YZ, et al. A Wnt and beta-catenin-dependent pathway for mammalian cardiac myogenesis. Proc Natl Acad Sci USA, 2003, 100(10):5834-5839.
18.	Naito AT, Akazawa H, Takano H, et al. Phosphatidylinositol 3-kinase-Akt pathway plays a critical role in early cardiomyogenesis by regu-lating canonical Wnt signaling. Circ Res, 2005, 97(2):144-151.
19.	高胜利. Wnt3a在胚胎干细胞向心肌细胞分化过程中的作用. 郑州:郑州大学, 2007.

1. Xu C, Police S, Rao N, et al. Characterization and enrichment of cardiomyocytes derived from human embryonic stem cells. Circ Res, 2002, 91(6):501-508.
2. Boheler KR, Czyz J, Tweedie D, et al. Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res, 2002, 91(3):189-201.
3. Caspi O, Huber I, Kehat I, et al. Transplantation of human embr-yonic stem cell-derived cardiomyocytes improves myocardial performance in infarcted rat hearts. J Am Coll Cardiol, 2007, 50 (19):1884-1893.
4. Fernandes S, Naumova AV, Zhu WZ, et al. Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats. J Mol Cell Cardiol, 2010, 49(6):941-949.
5. Matar AA, Chong JJ. Stem cell therapy for cardiac dysfunction.Springerplus, 2014, 3:440.
6. Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell:entity or function? Cell, 2001, 105(7):829-841.
7. Fu JD, Srivastava D. Direct reprogramming of fibroblasts into cardiomyocytes for cardiac regenerative medicine. Circ J, 2015, 79(2):245-254.
8. Boheler KR, Czyz J, Tweedie D, et al. Differentiation of pluripotent embryonic stem cells into cardiomyocytes. Circ Res, 2002, 91(3):189-201.
9. Jasmin D, Spray C, Campos DC, et al. Chemical induction of cardiac differentiation in p19 embryonal carcinoma stem cells. Stem Cells Dev, 2010, 19(3):403-412.
10. Wu YJ, Chen SY, Chang SJ, et al. Enhanced differentiation of rat MSCs into cardiomyocytes with 5-azacytidine/collagen I nano-molecules. Conf Proc IEEE Eng Med Biol Soc, 2013, 2013:322-325.
11. Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol, 2004, 20:781-810.
12. Ross SE, Hemati N, Longo KA, et al. Inhibition of adipogenesis by Wnt signaling. Science, 2000, 289(5481):950-953.
13. Moon RT, Kohn AD, De Ferrari GV, et al. WNT and beta-catenin signalling:diseases and therapies. Nat Rev Genet, 2004, 5(9):691-701.
14. Kuhl M, Geis K, Sheldahl LC, et al. Antagonistic regulation of convergent extension movements in Xenopus by Wnt/beta-catenin and Wnt/Ca2+ signaling. Mech Dev, 2001, 106(1-2):61-76.
15. Maye P, Zheng J, Li L, et al. Multiple mechanisms for Wnt11-mediated repression of the canonical Wnt signaling pathway. J Biol Chem, 2004, 279(23):24659-24665.
16. Eisenberg LM, Eisenberg CA. Wnt signal transduction and the formation of the myocardium. Dev Biol, 2006, 293(2):305-315.
17. Nakamura T, Sano M, Song YZ, et al. A Wnt and beta-catenin-dependent pathway for mammalian cardiac myogenesis. Proc Natl Acad Sci USA, 2003, 100(10):5834-5839.
18. Naito AT, Akazawa H, Takano H, et al. Phosphatidylinositol 3-kinase-Akt pathway plays a critical role in early cardiomyogenesis by regu-lating canonical Wnt signaling. Circ Res, 2005, 97(2):144-151.
19. 高胜利. Wnt3a在胚胎干细胞向心肌细胞分化过程中的作用. 郑州:郑州大学, 2007.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Experimental Research of Small Molecule Compound XAV939 Inducing Mouse Embryonic Stem Cell into Cardiac Myocyte

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