Hao Tong, Zhou Jin, Lü Shuanghong, Yang Boguang, Wang Yan, Fang Wancai, Jiang Xiaoxia, Lin Qiuxia, Li Junjie, Wang Changyong
School of Life Science and Technology, Harbin Institute of Technology, Harbin, People's Republic of China; Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, People's Republic of China.
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, People's Republic of China.
Int J Nanomedicine. 2016 Jan 18;11:269-83. doi: 10.2147/IJN.S95863. eCollection 2016.
Zero-dimensional fullerenes can modulate the biological behavior of a variety of cell lines. However, the effects and molecular mechanisms of proliferation and cardiomyogenic differentiation in brown adipose-derived stem cells (BADSCs) are still unclear. In this study, we report the initial biological effects of fullerene-C60 on BADSCs at different concentrations. Results suggest that fullerene-C60 has no cytotoxic effects on BADSCs even at a concentration of 100 μg/mL. Fullerene-C60 improves the MAPK expression level and stem cell survival, proliferation, and cardiomyogenesis. Further, we found that the fullerene-C60 modulates cardiomyogenic differentiation. Fullerene-C60 improves the expression of cardiomyocyte-specific proteins (cTnT and α-sarcomeric actinin). At elevated concentration, fullerene-C60 reduces the incidence of diminished spontaneous cardiac differentiation of BADSCs with time. At the genetic level, fullerene-C60 (5 μg/mL) also improves the expression of cTnT. In addition, fullerene-C60 promotes the formation of gap junction among cells. These findings have important implications for clinical application of fullerenes in the treatment of myocardial infarction.
零维富勒烯能够调节多种细胞系的生物学行为。然而，其对棕色脂肪来源干细胞（BADSCs）增殖和心肌分化的影响及分子机制仍不清楚。在本研究中，我们报告了不同浓度的富勒烯-C60对BADSCs的初始生物学效应。结果表明，即使在浓度为100μg/mL时，富勒烯-C60对BADSCs也没有细胞毒性作用。富勒烯-C60可提高丝裂原活化蛋白激酶（MAPK）表达水平以及干细胞的存活、增殖和心肌生成能力。此外，我们发现富勒烯-C60可调节心肌分化。富勒烯-C60能提高心肌细胞特异性蛋白（肌钙蛋白T（cTnT）和α-肌动蛋白）的表达。在较高浓度下，富勒烯-C60可降低BADSCs随时间自发心脏分化减少的发生率。在基因水平上，富勒烯-C60（5μg/mL）也能提高cTnT的表达。此外，富勒烯-C60可促进细胞间缝隙连接的形成。这些发现对于富勒烯在心肌梗死治疗中的临床应用具有重要意义。
