Differentiation of cardiomyocyte-like cells from human umbilical cord-derived mesenchymal stem cells induced by valsartan

doi:10.3969/j.issn.0529-1356.2014.06.019

Abstract

Abstract:

Objective To explore the feasibility of differentiating the human umbilical cord-derived msenchymal stem cells (hUCMSCs) to myocardiocyte-like cells after induction with valsartan. Methods The hUCMSCs were induced by valsartan and cultured for 1 week, 2 weeks and 3 weeks respectively. The antibodies against cardiac troponin T (cTnT）and recombinant GATA binding protein 4 (GATA4）were used to identify the cells which were induced to differentiate by immunocytochemistry and immunofluorescence. The mRNA expressions of cardiac troponin I(cTnI), myocardial-related transcription factor and myocardial development-related genes were detected by RT-PCR to identify the feasibility of differentiating hUCMSCs and inducing capacity of valsartan. Results The morphology of normal hUCMSCs showed uniform fibrous and whirlpool-like shape. They became significantly smaller and short spindle shape after valsartan induction. Immunochemical and immunofluorescence results showed that the expression of cTnT and GATA4 protein in the induced group was positive and seldom in the control group. RT-PCR results showed that the mRNA expression of cardiac-related transcription factor Tbx5, GATA4 and Nkx2.5 was spontaneously and continuously in the hUCMSCs. They increased after being induced by valsartan 1 week and then declined. The mRNA expression of cTnI was detected at 3 weeks, but the atrial natriuretic polypeptide（ANP）and β-myosin heavy chain (β-MHC) were not detected. Conclusion The hUCMSCs have capacity to be induced to differentiate into cardiomyocyte-like cells by valsartan.

Key words:

Valsartan, Inducation, Differentiation, Cardiomyocyte-like cell, Immunohistochemistry, Immunofluorescence, Human umbilical cord-derived msenchymal stem cell

HE Wan-li LI Yong-hai YANG Jun-zheng LIN Jun-tang GUO Zhi-kun XU Zhen-ping*. Differentiation of cardiomyocyte-like cells from human umbilical cord-derived mesenchymal stem cells induced by valsartan[J]. AAS, 2014, 45(6): 841-846.

References

［1］Kadivar M, Khatami S, Mortazavi Y, et al. In vitro cardiomyogenic potential of human umbilical vein-derived mesenchymal stem cells［J］. Biochem Biophys Res Commun, 2006, 340(2): 639-647.
［2］Qian Q, Qian H, Zhang X, et al.5-Azacytidine induces cardiac differentiation of human umbilical cord-derived mesenchymal stem cells by activating extracellular regulated kinase［J］. Stem Cells Dev, 2012, 21(1):67-75.
［3］Lin XB, He HY, Luo MJ, et al. Differentiation of human umbilical cord-derived mesenchymal stem cells into cardiomyocytes［J］. Journal of Applied Clinical Pediatrics, 2007, 22(13):971-973.(in Chinese)
    林晓波，何红燕，罗敏洁，等.人脐带间充质干细胞向心肌样细胞分化的研究［J］. 实用儿科临床杂志，2007，22（13）：971-973.
［4］Shim WS, Jiang S, Wong P, et al. Ex vivo differentiation of human adult bone marrow stem cells into cardiomyocyte-like cells［J］. Biochem Biophys Res Commun, 2004, 324(2): 481-488.
［5］Yoon J, Min BG, Kim YH, et al. Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model［J］. Acta Cardiol, 2005, 60(3): 277-284.
［6］Perán M, Marchal JA, López E, et al. Human cardiac tissue induces transdifferentiation of adult stem cells towards cardiomyocytes［J］. Cytotherapy, 2010, 12(3): 332-337.
［7］Shinmura D, Togashi I, Miyoshi S, et al. Pretreatment of human mesenchymal stem cells with pioglitazone improved efficiency of cardiomyogenic transdifferentiation and cardiac function［J］. Stem Cells, 2011, 29(2):357-366.
［8］Numasawa Y, Kimura T, Miyoshi S, et al. Treatment of human mesenchymal stem cells with angiotensin receptor blocker improved efficiency of cardiomyogenic transdifferentiation and improved cardiac function via angiogenesis［J］. Stem Cells, 2011, 29(9):1405-1414.
［9］Yoon JH, Roh EY, Shin S, et al. Introducing pulsed low-intensity ultrasound to culturing human umbilical cord-derived mesenchymal stem cells［J］. Biotechnol Lett, 2009, 31(3): 329-335.
［10］Jo CH, Kim OS, Park EY, et al. Fetal mesenchymal stem cells derived from human umbilical cord sustain primitive characteristics during extensive expansion［J］. Cell Tissue Res, 2008, 334(3): 423-433.
［11］Ishige I, Nagamura-Inoue T, Honda MJ, et al. Comparison of mesenchymal stem cells derived from arterial, venous, and Wharton’s jelly explants of human umbilical cord［J］. Int J Hematol, 2009, 90(2): 261-269.
［12］Campard D, Lysy PA, Najimi M, et al. Native umbilical cord matrix stem cells express hepatic markers and differentiation into hepatocute-like cells［J］. Gastroenterology, 2008, 134(3): 833-848.
［13］Wu LF, Wang NN, Liu YS, et al. Differentiation of Wharton’s jelly primitive stromal cells into insulin-producing cells in comparison with bone marrow mesenchymal stem cells［J］. Tissue Eng Part A, 2009, 15(10): 2865-2873.
［14］Huang P, Lin LM, Wu XY, et al. Differentiation of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells into germ-like cells in vitro［J］. Cell biochem, 2010, 109(4): 747-754.
［15］Zhang WZ, Wang ZhG, Chen YQ, et al. Effects of valsartan and U0126 on atrial fibrosis and connexin40 remodeling in rats［J］. Chinese Journal of Cardiology, 2011, 39(12):1129-1134.(in Chinese)
     张卫泽，王智刚，陈永清，等.缬沙坦与U0126对大鼠心房纤维化和缝隙连接蛋白40重构的影响［J］.中华心血管病杂志，2011，39（12）：1129-1134.
［16］Gong LG, Qiu GR, Xu XY, et al. Advances of heart-specific trafcription factors: NKX2-5, TBX5 and GATA4 in congenital heart disease［J］. International Journal of Genetics, 2006, 29(2):133-136.(in Chinese)
     宫立国，邱广荣，徐小延，等.心脏特异转录因子Nkx25、TBX5、GATA4与先天性心脏病的研究进展［J］. 国际遗传学杂志，2006，29（2）：133-136.
［17］Galli D, Gobbi G, Carrubbi C, et al. The role of PKCε-dependent signaling for cardiac differentiation［J］. Histochem Cell Biol, 2013, 139(1):35-46.
［18］Yan XB, Li Q , Guo ZhK, et al. Biological phenotypes of rabbit adipose-derived mesenchymal stem cells and their differentiation potentiality for myocardiocyte-like cells［J］. Acta Anatomica Sinica, 2013,44(1):55-61.(in Chinese)
     闫小宾，李琼，郭志坤，等.兔脂肪来源间充质干细胞的生物表型及其心肌样细胞的分化潜能［J］. 解剖学报，2013，44（1）：55-61.

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