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不同剂量的骨形态发生蛋白4(BMP4)可刺激脂肪来源干细胞向心房和心室方向分化。

Atrial and ventricular specification of ADSCs is stimulated by different doses of BMP4.

作者信息

Khaleghi Maryam, Taha Masoumeh Fakhr, Jafarzadeh Nazli, Javeri Arash

机构信息

Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), P.O. Box: 14965-161, Tehran, Iran.

出版信息

Biotechnol Lett. 2014 Dec;36(12):2581-9. doi: 10.1007/s10529-014-1637-8. Epub 2014 Sep 13.

DOI:10.1007/s10529-014-1637-8
PMID:25216643
Abstract

To investigate the effect of BMP4 on cardiomyocyte differentiation of adipose tissue-derived stem cells (ADSCs), mouse ADSCs were treated with different concentrations of BMP4 in media containing fetal bovine serum (FBS) or Knockout™ Serum Replacement (KoSR). 3 weeks after cardiac induction, differentiated ADSCs expressed some cardiac-specific genes and proteins. BMP4 treatment upregulated the expression of cardiac transcription factors. In both FBS and KoSR-supplemented media, lower concentrations of BMP4 had a positive effect on the expression of MLC2A gene, while MLC2V was more expressed with higher concentrations of BMP4. BMP4 treatment in KoSR supplemented medium was more efficient for cardiac induction. Supplementation of culture media with insulin-transferrin-selenium improved the expression of MLC2A gene. The results of this study indicated that BMP4 is important for cardiac differentiation of the ADSCs. However, BMP4 was not enough for structural and functional maturation of the ADSC-derived cardiomyocytes.

摘要

为研究骨形态发生蛋白4(BMP4)对脂肪组织来源干细胞(ADSCs)向心肌细胞分化的影响,在含有胎牛血清(FBS)或Knockout™血清替代物(KoSR)的培养基中,用不同浓度的BMP4处理小鼠ADSCs。心脏诱导3周后,分化的ADSCs表达了一些心脏特异性基因和蛋白质。BMP4处理上调了心脏转录因子的表达。在FBS和添加了KoSR的培养基中,较低浓度的BMP4对肌球蛋白轻链2A(MLC2A)基因的表达有积极影响,而较高浓度的BMP4时肌球蛋白轻链2V(MLC2V)表达更多。在添加了KoSR的培养基中进行BMP4处理对心脏诱导更有效。培养基中添加胰岛素-转铁蛋白-硒可改善MLC2A基因的表达。本研究结果表明,BMP4对ADSCs的心脏分化很重要。然而,BMP4不足以使ADSC来源的心肌细胞实现结构和功能成熟。

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Differentiation of brown adipose-derived stem cells into cardiomyocyte-like cells is regulated by a combination of low 5-azacytidine concentration and bone morphogenetic protein 4.棕色脂肪来源干细胞向心肌样细胞的分化受低浓度5-氮杂胞苷和骨形态发生蛋白4共同调控。
Int J Clin Exp Pathol. 2018 Nov 1;11(11):5514-5524. eCollection 2018.
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Cardiac Differentiation of Adipose Tissue-Derived Stem Cells Is Driven by BMP4 and bFGF but Counteracted by 5-Azacytidine and Valproic Acid.
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Iran J Basic Med Sci. 2017 Nov;20(11):1200-1206. doi: 10.22038/IJBMS.2017.9464.