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The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells.
Stem Cells Dev. 2014 Jun 15; 23(12):1364-76.SC

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.

Authors+Show Affiliations

1 Department of Applied Bioscience, CHA University , Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24524758

Citation

Kim, Ji Hye, et al. "The Molecular Mechanism Underlying the Proliferating and Preconditioning Effect of Vitamin C On Adipose-derived Stem Cells." Stem Cells and Development, vol. 23, no. 12, 2014, pp. 1364-76.
Kim JH, Kim WK, Sung YK, et al. The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells. Stem Cells Dev. 2014;23(12):1364-76.
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), 1364-76. https://doi.org/10.1089/scd.2013.0460
Kim JH, et al. The Molecular Mechanism Underlying the Proliferating and Preconditioning Effect of Vitamin C On Adipose-derived Stem Cells. Stem Cells Dev. 2014 Jun 15;23(12):1364-76. PubMed PMID: 24524758.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells. AU - Kim,Ji Hye, AU - Kim,Wang-Kyun, AU - Sung,Young Kwan, AU - Kwack,Mi Hee, AU - Song,Seung Yong, AU - Choi,Joon-Seok, AU - Park,Sang Gyu, AU - Yi,TacGhee, AU - Lee,Hyun-Joo, AU - Kim,Dae-Duk, AU - Seo,Hyun Min, AU - Song,Sun U, AU - Sung,Jong-Hyuk, Y1 - 2014/03/21/ PY - 2014/2/15/entrez PY - 2014/2/15/pubmed PY - 2015/2/13/medline SP - 1364 EP - 76 JF - Stem cells and development JO - Stem Cells Dev VL - 23 IS - 12 N2 - 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. SN - 1557-8534 UR - https://www.unboundmedicine.com/medline/citation/24524758/The_molecular_mechanism_underlying_the_proliferating_and_preconditioning_effect_of_vitamin_C_on_adipose_derived_stem_cells_ L2 - https://www.liebertpub.com/doi/10.1089/scd.2013.0460?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -