The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells

Ji Hye Kim, Wang Kyun Kim, Young Kwan Sung, Mi Hee Kwack, Seung Yong Song, Joon Seok Choi, Sang Gyu Park, Tacghee Yi, Hyun Joo Lee, Dae Duk Kim, Hyun Min Seo, Sun U. Song, Jong Hyuk Sung

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Abstract

Although adipose-derived stem cells (ASCs) show promise for cell therapy, there is a tremendous need for developing ASC activators. In the present study, we investigated whether or not vitamin C increases the survival, proliferation, and hair-regenerative potential of ASCs. In addition, we tried to find the molecular mechanisms underlying the vitamin C-mediated stimulation of ASCs. Sodium-dependent vitamin C transporter 2 (SVCT2) is expressed in ASCs, and mediates uptake of vitamin C into ASCs. Vitamin C increased the survival and proliferation of ASCs in a dose-dependent manner. Vitamin C increased ERK1/2 phosphorylation, and inhibition of the mitogen-activated protein kinase (MAPK) pathway attenuated the proliferation of ASCs. Microarray and quantitative polymerase chain reaction showed that vitamin C primarily upregulated expression of proliferation-related genes, including Fos, E2F2, Ier2, Mybl1, Cdc45, JunB, FosB, and Cdca5, whereas Fos knock-down using siRNA significantly decreased vitamin C-mediated ASC proliferation. In addition, vitamin C-treated ASCs accelerated the telogen-to-anagen transition in C3H/HeN mice, and conditioned medium from vitamin C-treated ASCs increased the hair length and the Ki67-positive matrix keratinocytes in hair organ culture. Vitamin C increased the mRNA expression of HGF, IGFBP6, VEGF, bFGF, and KGF, which may mediate hair growth promotion. In summary, vitamin C is transported via SVCT2, and increased ASC proliferation is mediated by the MAPK pathway. In addition, vitamin C preconditioning enhanced the hair growth promoting effect of ASCs. Because vitamin C is safe and effective, it could be used to increase the yield and regenerative potential of ASCs.

Original languageEnglish
Pages (from-to)1364-1376
Number of pages13
JournalStem Cells and Development
Volume23
Issue number12
DOIs
Publication statusPublished - 2014 Jun 15

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All Science Journal Classification (ASJC) codes

  • Hematology
  • Developmental Biology
  • Cell Biology

Cite this

Kim, J. H., Kim, W. K., Sung, Y. K., Kwack, M. H., Song, S. Y., Choi, J. S., Park, S. G., Yi, T., Lee, H. J., Kim, D. D., Seo, H. M., Song, S. U., & Sung, J. H. (2014). The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells. Stem Cells and Development, 23(12), 1364-1376. https://doi.org/10.1089/scd.2013.0460