首页> 美国卫生研究院文献>Stem Cells International >Differentiation of Bone Marrow Mesenchymal Stem Cells to Cardiomyocyte-Like Cells Is Regulated by the Combined Low Dose Treatment of Transforming Growth Factor-β1 and 5-Azacytidine
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Differentiation of Bone Marrow Mesenchymal Stem Cells to Cardiomyocyte-Like Cells Is Regulated by the Combined Low Dose Treatment of Transforming Growth Factor-β1 and 5-Azacytidine

机译:转化生长因子-β1和5-氮杂胞苷的低剂量联合治疗可调节骨髓间充质干细胞向心肌样细胞的分化

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摘要

Bone marrow mesenchymal stem cells (BMMSCs) are used in cardiac tissue engineering for the regeneration of diseased hearts. We examined the differentiation of rat BMMSCs into cardiomyocyte-like cells when induced with a combined low dose treatment of transforming growth factor-β1 (TGF-β1) and 5-azacytidine (5-AZA). Results showed that cell proliferation in the combined low dose treatment group of TGF-β1 and 5-AZA was increased compared with the TGF-β1 group or the 5-AZA group. The cell apoptosis was relieved by combined TGF-β1 and 5-AZA treatment compared to 5-AZA treatment alone. The number of cells positive for myosin heavy chain, connexin-43, α-actin, and troponin I in the combined treatment group was higher than those observed in the TGF-β1 group or the 5-AZA group. Moreover, the combined low dose treatment group of TGF-β1 and 5-AZA reveals the strongest expression of troponin I, α-actin, and phosphorylated extracellular signal-regulated protein kinases 1 and 2 (p-ErK1/2) among the treatment groups. These results suggest that the combined low dose treatment of TGF-β1 and 5-AZA can improve the differentiation potential of rat BMMSCs into cardiomyocyte-like cells and alleviate cell damage effects in vitro. The mechanism that is involved in influencing differentiation may be associated with p-ErK1/2.
机译:骨髓间充质干细胞(BMMSC)用于心脏组织工程中,以再生患病的心脏。我们用转化生长因子-β1(TGF-β1)和5-氮杂胞苷(5-AZA)的联合低剂量治疗诱导了大鼠骨髓间充质干细胞向心肌样细胞的分化。结果显示,与TGF-β1组或5-AZA组相比,TGF-β1和5-AZA联合低剂量治疗组的细胞增殖增加。与单独的5-AZA处理相比,通过联合TGF-β1和5-AZA处理可减轻细胞凋亡。联合治疗组中肌球蛋白重链,连接蛋白-43,α-肌动蛋白和肌钙蛋白I阳性的细胞数高于TGF-β1组或5-AZA组。此外,TGF-β1和5-AZA的低剂量联合治疗组显示了肌钙蛋白I,α-肌动蛋白以及磷酸化的细胞外信号调节蛋白激酶1和2(p-ErK1 / 2)的最强表达。 。这些结果表明,TGF-β1和5-AZA的低剂量联合治疗可提高大鼠骨髓间充质干细胞向心肌样细胞的分化潜能,并减轻体外细胞损伤作用。影响分化的机制可能与p-ErK1 / 2有关。

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