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Resveratrol Exerts Dosage-Dependent Effects on the Self-Renewal and Neural Differentiation of hUC-MSCs
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  • Journal title : Molecules and Cells
  • Volume 39, Issue 5,  2016, pp.418-425
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2016.2345
 Title & Authors
Resveratrol Exerts Dosage-Dependent Effects on the Self-Renewal and Neural Differentiation of hUC-MSCs
Wang, Xinxin; Ma, Shanshan; Meng, Nan; Yao, Ning; Zhang, Kun; Li, Qinghua; Zhang, Yanting; Xing, Qu; Han, Kang; Song, Jishi; Yang, Bo; Guan, Fangxia;
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 Abstract
Resveratrol (RES) plays a critical role in the fate of cells and longevity of animals via activation of the sirtuins1 (SIRT1) gene. In the present study, we intend to investigate whether RES could promote the self-renewal and neural-lineage differentiation in human umbilical cord derived MSCs (hUC-MSCs) in vitro at concentrations ranging from 0.1 to , and whether it exerts the effects by modulating the SIRT1 signaling. Herein, we demonstrated that RES at the concentrations of 0.1, 1 and could promote cell viability and proliferation, mitigate senescence and induce expression of SIRT1 and Proliferating Cell Nuclear Antigen (PCNA) while inhibit the expression of p53 and p16. However, the effects were reversed by 5 and of RES. Furthermore, RES could promote neural differentiation in a dose-dependent manner as evidenced by morphological changes and expression of neural markers (Nestin, and NSE), as well as pro-neural transcription factors Neurogenin (Ngn)1, Ngn2 and Mash1. Taken together, RES exerts a dosage-dependent effect on the self-renewal and neural differentiation of hUC-MSCs via SIRT1 signaling. The current study provides a new strategy to regulate the fate of hUC-MSCs and suggests a more favorable in vitro cell culture conditions for hUCMSCs-based therapies for some intractable neurological disorders.
 Keywords
human umbilical cord derived mesenchymal stem cells;neural differentiation;resveratrol;self-renewal;SIRT1;
 Language
English
 Cited by
1.
Resveratrol enhances the radiosensitivity of nasopharyngeal carcinoma cells by downregulating E2F1, Oncology Reports, 2017, 37, 3, 1833  crossref(new windwow)
 References
1.
Atkins, K.M., Thomas, L.L., Barroso-Gonzalez, J., Thomas, L., Auclair, S., Yin, J., Kang, H., Chung, J.H., Dikeakos, J.D., and Thomas, G. (2014). The multifunctional sorting protein PACS-2 regulates SIRT1-mediated deacetylation of p53 to modulate p21-dependent cell-cycle arrest. Cell Rep. 8, 1545-1557. crossref(new window)

2.
Can, A., and Karahuseyinoglu, S. (2007). Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells 25, 2886-2895. crossref(new window)

3.
Cardozo, A.J., Gomez, D.E., and Argibay, P.F. (2012). Neurogenic differentiation of human adipose-derived stem cells: relevance of different signaling molecules, transcription factors, and key marker genes. Gene 511, 427-436. crossref(new window)

4.
Chen, H., Liu, X., Chen, H., Cao, J., Zhang, L., Hu, X., and Wang, J. (2014a). Role of SIRT1 and AMPK in mesenchymal stem cells differentiation. Ageing Res. Rev. 13, 55-64. crossref(new window)

5.
Chen, H., Liu, X., Zhu, W., Chen, H., Hu, X., Jiang, Z., Xu, Y., Wang, L., Zhou, Y., Chen, P., et al. (2014b). SIRT1 ameliorates agerelated senescence of mesenchymal stem cells via modulating telomere shelterin. Front Aging Neurosci. 6, 103.

6.
Chen, B., Zang, W., Wang, J., Huang, Y., He, Y., Yan, L., Liu, J., and Zheng, W. (2015). The chemical biology of sirtuins. Chem. Soc. Rev. 44, 5246-5264. crossref(new window)

7.
da Luz, P.L., Tanaka, L., Brum, P.C., Dourado, P.M., Favarato, D., Krieger, J.E., and Laurindo, F.R. (2012). Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats. Atherosclerosis 224, 136-142. crossref(new window)

8.
Dai, Z., Li, Y., Quarles, L.D., Song, T., Pan, W., Zhou, H., and Xiao, Z. (2007). Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. Phytomedicine 14, 806-814. crossref(new window)

9.
Godoy, J.A., Zolezzi, J.M., Braidy, N., and Inestrosa, N.C. (2014). Role of Sirt1 during the ageing process: relevance to protection of synapses in the brain. Mol. Neurobiol. 50, 744-756. crossref(new window)

10.
Guo, R., Li, W., Liu, B., Li, S., Zhang, B., and Xu, Y. (2014). Resveratrol protects vascular smooth muscle cells against high glucose-induced oxidative stress and cell proliferation in vitro. Med. Sci. Monit Basic Res. 20, 82-92. crossref(new window)

11.
Heng, B.C., Saxena, P., and Fussenegger, M. (2014). Heterogeneity of baseline neural marker expression by undifferentiated mesenchymal stem cells may be correlated to donor age. J. Biotechnol. 174, 29-33. crossref(new window)

12.
Hisahara, S., Chiba, S., Matsumoto, H., Tanno, M., Yagi, H., Shimohama, S., Sato, M., and Horio, Y. (2008). Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation. Proc. Natl. Acad. Sci. USA 105, 15599-15604. crossref(new window)

13.
Hubbard, B.P., and Sinclair, D.A. (2014). Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol. Sci. 35, 146-154. crossref(new window)

14.
Ido, Y., Duranton, A., Lan, F., Weikel, K.A., Breton, L., and Ruderman, N.B. (2015). Resveratrol prevents oxidative stressinduced senescence and proliferative dysfunction by activating the AMPK-FOXO3 cascade in cultured primary human keratinocytes. PLoS One 10, e0115341. crossref(new window)

15.
Jackson, S.J., Singletary, K.W., Murphy, L.L., Venema, R.C., and Young, A.J. (2016). Phytonutrients differentially stimulate NAD(P)H:quinone oxidoreductase, inhibit proliferation, and trigger mitotic catastrophe in Hepa1c1c7 cells. J. Med. Food 19, 47-53. crossref(new window)

16.
Joe, I.S., Jeong, S.G., and Cho, G.W. (2015). Resveratrol-induced SIRT1 activation promotes neuronal differentiation of human bone marrow mesenchymal stem cells. Neurosci. Lett. 584, 97-102. crossref(new window)

17.
Karahuseyinoglu, S., Cinar, O., Kilic, E., Kara, F., Akay, G.G., Demiralp, D.O., Tukun, A., Uckan, D., and Can, A. (2007). Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys. Stem Cells 25, 319-331. crossref(new window)

18.
Kumazaki, M., Noguchi, S., Yasui, Y., Iwasaki, J., Shinohara, H., Yamada, N., and Akao, Y. (2013). Anti-cancer effects of naturally occurring compounds through modulation of signal transduction and miRNA expression in human colon cancer cells. J. Nutr. Biochem. 24, 1849-1858. crossref(new window)

19.
Lee, J.K., Jin, H.K., Endo, S., Schuchman, E.H., Carter, J.E., and Bae, J.S. (2010). Intracerebral transplantation of bone marrow-derived mesenchymal stem cells reduces amyloid-beta deposition and rescues memory deficits in Alzheimer's disease mice by modulation of immune responses. Stem Cells 28, 329-343.

20.
Liu, B., Ghosh, S., Yang, X., Zheng, H., Liu, X., Wang, Z., Jin, G., Zheng, B., Kennedy, B.K., Suh, Y., et al. (2012). Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metab. 16, 738-750. crossref(new window)

21.
Luo, J., Nikolaev, A.Y., Imai, S., Chen, D., Su, F., Shiloh, A., Guarente, L., and Gu, W. (2001). Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107, 137-148. crossref(new window)

22.
Ma, S., Liang, S., Jiao, H., Chi, L., Shi, X., Tian, Y., Yang, B., and Guan, F. (2014). Human umbilical cord mesenchymal stem cells inhibit C6 glioma growth via secretion of dickkopf-1 (DKK1). Mol. Cell Biochem. 385, 277-286. crossref(new window)

23.
Marambaud, P., Zhao, H., and Davies, P. (2005). Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides. J. Biol. Chem. 280, 37377-37382. crossref(new window)

24.
Mikula-Pietrasik, J., Kuczmarska, A., Rubis, B., Filas, V., Murias, M., Zielinski, P., Piwocka, K., and Ksiazek, K. (2012). Resveratrol delays replicative senescence of human mesothelial cells via mobilization of antioxidative and DNA repair mechanisms. Free Radic. Biol. Med. 52, 2234-2245. crossref(new window)

25.
Ozcan, P., Ficicioglu, C., Yildirim, O.K., Ozkan, F., Akkaya, H., and Aslan, I. (2015). Protective effect of resveratrol against oxidative damage to ovarian reserve in female Sprague-Dawley rats. Reprod. Biomed. Online 31, 404-410. crossref(new window)

26.
Park, H.R., Kong, K.H., Yu, B.P., Mattson, M.P., and Lee, J. (2012). Resveratrol inhibits the proliferation of neural progenitor cells and hippocampal neurogenesis. J. Biol. Chem. 287, 42588-42600. crossref(new window)

27.
Pinarli, F.A., Turan, N.N., Pinarli, F.G., Okur, A., Sonmez, D., Ulus, T., Oguz, A., Karadeniz, C., and Delibasi, T. (2013). Resveratrol and adipose-derived mesenchymal stem cells are effective in the prevention and treatment of doxorubicin cardiotoxicity in rats. Pediatr. Hematol. Oncol. 30, 226-238. crossref(new window)

28.
Rathbone, C.R., Booth, F.W., and Lees, S.J. (2009). Sirt1 increases skeletal muscle precursor cell proliferation. Eur. J. Cell Biol. 88, 35-44. crossref(new window)

29.
Rehan, L., Laszki-Szczachor, K., Sobieszczanska, M., and Polak-Jonkisz, D. (2014). SIRT1 and NAD as regulators of ageing. Life Sci. 105, 1-6. crossref(new window)

30.
Rimmele, P., Lofek-Czubek, S., and Ghaffari, S. (2014). Resveratrol increases the bone marrow hematopoietic stem and progenitor cell capacity. Am. J. Hematol. 89, E235-238. crossref(new window)

31.
Saharan, S., Jhaveri, D.J., and Bartlett, P.F. (2013). SIRT1 regulates the neurogenic potential of neural precursors in the adult subventricular zone and hippocampus. J. Neurosci. Res. 91, 642-659. crossref(new window)

32.
Simic, P., Zainabadi, K., Bell, E., Sykes, D.B., Saez, B., Lotinun, S., Baron, R., Scadden, D., Schipani, E., and Guarente, L. (2013). SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating beta-catenin. EMBO Mol. Med. 5, 430-440. crossref(new window)

33.
Song, L.H., Pan, W., Yu, Y.H., Quarles, L.D., Zhou, H.H., and Xiao, Z.S. (2006). Resveratrol prevents CsA inhibition of proliferation and osteoblastic differentiation of mouse bone marrow-derived mesenchymal stem cells through an ER/NO/cGMP pathway. Toxicol. In Vitro 20, 915-922. crossref(new window)

34.
Tsai, J.H., Hsu, L.S., Lin, C.L., Hong, H.M., Pan, M.H., Way, T.D., and Chen, W.J. (2013). 3,5,4'-Trimethoxystilbene, a natural methoxylated analog of resveratrol, inhibits breast cancer cell invasiveness by downregulation of PI3K/Akt and Wnt/betacatenin signaling cascades and reversal of epithelialmesenchymal transition. Toxicol. Appl. Pharmacol. 272, 746-756. crossref(new window)

35.
Vassallo, P.F., Simoncini, S., Ligi, I., Chateau, A.L., Bachelier, R., Robert, S., Morere, J., Fernandez, S., Guillet, B., Marcelli, M., et al. (2014). Accelerated senescence of cord blood endothelial progenitor cells in premature neonates is driven by SIRT1 decreased expression. Blood 123, 2116-2126. crossref(new window)

36.
Yu, Q., Liu, L., Duan, Y., Wang, Y., Xuan, X., Zhou, L., and Liu, W. (2013). Wnt/beta-catenin signaling regulates neuronal differentiation of mesenchymal stem cells. Biochem. Biophys. Res. Commun. 439, 297-302. crossref(new window)

37.
Yuan, H.F., Zhai, C., Yan, X.L., Zhao, D.D., Wang, J.X., Zeng, Q., Chen, L., Nan, X., He, L.J., Li, S.T., et al. (2012). SIRT1 is required for long-term growth of human mesenchymal stem cells. J. Mol. Med. (Berl). 90, 389-400. crossref(new window)

38.
Zhang, D.Y., Wang, H.J., and Tan, Y.Z. (2011). Wnt/beta-catenin signaling induces the aging of mesenchymal stem cells through the DNA damage response and the p53/p21 pathway. PLoS One 6, e21397. crossref(new window)

39.
Zhang, T., Tian, F., Wang, J., Zhou, S., Dong, X., Guo, K., Jing, J., Zhou, Y., and Chen, Y. (2015). Donepezil attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells through SIRT1 activation. Cell Stress Chaperones 20, 787-792. crossref(new window)

40.
Zhu, Y., He, W., Gao, X., Li, B., Mei, C., Xu, R., and Chen, H. (2015). Resveratrol overcomes gefitinib resistance by increasing the intracellular gefitinib concentration and triggering apoptosis, autophagy and senescence in PC9/G NSCLC cells. Sci Rep. 5, 17730. crossref(new window)

41.
Zhu, X., Zhang, Y., Li, Q., Yang, L., Zhang, N., Ma, S., Zhang, K., Song, J. and Guan, F. (2016). ${\beta}$-carotene induces apoptosis in human esophageal squamous cell carcinoma cell lines via the Cav-1/AKT/NF-kappaB signaling pathway. J. Biochem. Mol. Toxicol. 30, 148-157. crossref(new window)