維生素對小鼠骨髓間質幹細胞的分化及免疫調節特性之影響

王資婷

doi:10.6342/NTU201703440

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维生素对小鼠骨髓间质干细胞的分化及免疫调节特性之影响

Effects of vitamins on the differentiation and immune regulatory properties of mouse bone marrow mesenchymal stem cells

王资婷 , 硕士　　导师：林璧凤　　

繁体中文 DOI： 10.6342/NTU201703440

间质干细胞；维生素A ；维生素D ；叶酸；脂肪细胞分化； Mesenchymal stem cells ； vitamin A ； vitamin D ； folic acid ； adipocyte differentiation

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摘要 │ 参考文献 (131) │ 国际计量

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Mesenchymal stem cells (MSCs) are multipotent stem cells which have regenerative and immunoregulatory properties. These features make MSCs being applied in cellular therapy an attractive approach. MSCs can differentiate into osteocytes, chondrocytes and adipocytes under certain culture condition. Recent studies have demonstrated that MSC might lose immunoregulatory properties during the adipogenic differentiation, suggesting its relationships with immunity. Vitamin A and D have been known to regulate the differentiation of MSCs, and might have effects on the immunoregulatory properties of MSCs. Hence, the aim of this study is to investigate the effects of vitamins on differentiation and immunoregulatory properties of MSCs. First, MSCs were isolated from 4-week-old BALB/c bone marrow, characterized by specific surface markers, differentiation tendency to adipocytes, chondrocytes and osteocytes under appropriate condition, and the immunoregulatory properties to supress T cells proliferation. After confirming all the above properties of MSCs, MSCs were cultrured in medium containing different concentrations of all trans-retinoic acid, 1α,25-(OH)2D3 and folic acid. Differentiation and immunoregulatory properties were determined on days 3, 7 and 14. These results showed that after a 7-day culture, vitamin A reduced the gene exprsesion of PPARγ, C/EBPα, Ap2, Glut4, and promoted the proliferation of MSCs. Vitamin D under 0.1 nM reduced the gene exprsesion of C/EBPα, Ap2, but also inhibited the proliferation of MSCs. Folic acid promoted the proliferation of MSCs and under 100 μM could reduce the expression of C/EBPα. On the other hand, all of these vitamins did not alter the inhibitory effect of MSC subsets on CD4+ T cell proliferation. Vitamin A and folic acid reduced the gene expression of Tnfα, Tgfb after a 7-day culture. Besides, Vitamin A enhanced the expression of Il-6 after a 14-day culture. In conclusion, Vitamin A could promote the proliferation of MSCs and inhibited the adipogenesis of MSCs. Vitamin D could inhibit the expression of adipocyte-related gene, but also inhibit the proliferation of MSCs. Folic acid could also promote the proliferation of MSCs, and maintain MSCs in an undifferentiated state. This research suggested that addition of vitamins at certain concentration might alter MSC proliferation and differentiation, which provides information for the expansion of MSCs.

参考文献 ( 131 ) 〈TOP〉

Abbas, M. A. (2017). Physiological functions of Vitamin D in adipose tissue. J Steroid Biochem Mol Biol 165(Pt B): 369-381.
连结：
Abe, I., Shirato, K., Hashizume, Y., Mitsuhashi, R., Kobayashi, A., Shiono, C., Sato, S., Tachiyashiki, K. and Imaizumi, K. (2013). Folate-deficiency induced cell-specific changes in the distribution of lymphocytes and granulocytes in rats. Environ Health Prev Med 18(1): 78-84.
连结：
Aggarwal, S. and Pittenger, M. F. (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105(4): 1815-1822.
连结：
Ahima, R. S. (2008). Revisiting leptin's role in obesity and weight loss. J Clin Invest 118(7): 2380-2383.
连结：
Augello, A., Tasso, R., Negrini, S. M., Amateis, A., Indiveri, F., Cancedda, R. and Pennesi, G. (2005). Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol 35(5): 1482-1490.
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引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。