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三碘-L-甲状腺原氨酸促进大鼠骨髓间充质干细胞来源的心肌细胞成熟。

Triiodo-L-Thyronine Promotes the Maturation of Cardiomyocytes Derived From Rat Bone Marrow Mesenchymal Stem Cells.

作者信息

Shi Shu-Tian, Wu Xing-Xin, Hao Wen, Wang Xiao, Miao Huang-Tai, Zhen Lei, Nie Shao-Ping

机构信息

*Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China; and †Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, China.

出版信息

J Cardiovasc Pharmacol. 2016 May;67(5):388-93. doi: 10.1097/FJC.0000000000000363.

Abstract

Bone marrow mesenchymal stem cells (BMMSCs) can differentiate into cardiomyocytes and be used in cardiac tissue engineering for heart regeneration. However, the effective clinical application of cardiomyocytes derived from BMMSCs is limited because of their immature phenotype. The aim of this study was to investigate the potential of triiodo-L-thyronine (T3) to drive cardiomyocytes derived from BMMSCs to a more mature state. BMMSCs were divided into 3 groups: untreated controls, differentiated, and T3 treated. The differentiation potential was evaluated by immunofluorescence microscopy and flow cytometry. Data were represented as the numbers of cells positive for the troponin I (cTnI), α-actinin, GATA4, and the connexin-43 (Cx-43). The mRNA levels of these specific markers of cardiomyocytes were determined by quantitative real-time polymerase chain reaction. The levels of cardiomyocytes markers protein and octamer-binding transcription factor 4 (Oct-4) were determined by Western blot analyses. Our data demonstrate that T3 treatment leads to a significant increase in cells positive for cTnI, GATA4, Cx-43, and α-actinin. The mRNA and protein expression levels of these specific markers of cardiomyocytes were also increased after T3 treatment. At the same time, the protein expression level of Oct-4 was substantially downregulated in T3-treated cells. These results demonstrate that T3 treatment increases the differentiation of BMMSCs induced to cardiomyocytes and promotes their maturation.

摘要

骨髓间充质干细胞(BMMSCs)可分化为心肌细胞,并用于心脏组织工程以实现心脏再生。然而,由于其未成熟的表型,源自BMMSCs的心肌细胞在临床上的有效应用受到限制。本研究的目的是探讨三碘-L-甲状腺原氨酸(T3)促使源自BMMSCs的心肌细胞向更成熟状态发展的潜力。将BMMSCs分为3组:未处理的对照组、分化组和T3处理组。通过免疫荧光显微镜和流式细胞术评估分化潜力。数据以肌钙蛋白I(cTnI)、α-肌动蛋白、GATA4和连接蛋白-43(Cx-43)阳性细胞的数量表示。通过定量实时聚合酶链反应测定这些心肌细胞特异性标志物的mRNA水平。通过蛋白质印迹分析测定心肌细胞标志物蛋白和八聚体结合转录因子4(Oct-4)的水平。我们的数据表明,T3处理导致cTnI、GATA4、Cx-43和α-肌动蛋白阳性细胞显著增加。T3处理后,这些心肌细胞特异性标志物的mRNA和蛋白表达水平也增加。同时,在T3处理的细胞中,Oct-4的蛋白表达水平大幅下调。这些结果表明,T3处理增加了诱导分化为心肌细胞的BMMSCs的分化,并促进了它们的成熟。

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