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

Research output: Contribution to journalArticle

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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

Fingerprint

Ascorbic Acid
Stem Cells
Hair
Sodium-Coupled Vitamin C Transporters
Mitogen-Activated Protein Kinases
Cell Proliferation
fos Genes
Inbred C3H Mouse
Organ Culture Techniques
Conditioned Culture Medium
Growth
Cell- and Tissue-Based Therapy
Keratinocytes
Vascular Endothelial Growth Factor A
Small Interfering RNA
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Hematology
  • Developmental Biology
  • Cell Biology

Cite this

Kim, Ji Hye ; Kim, Wang Kyun ; Sung, Young Kwan ; Kwack, Mi Hee ; Song, Seung Yong ; Choi, Joon Seok ; Park, Sang Gyu ; Yi, Tacghee ; Lee, Hyun Joo ; Kim, Dae Duk ; Seo, Hyun Min ; Song, Sun U. ; Sung, Jong Hyuk. / The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells. In: Stem Cells and Development. 2014 ; Vol. 23, No. 12. pp. 1364-1376.
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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.",
author = "Kim, {Ji Hye} and Kim, {Wang Kyun} and Sung, {Young Kwan} and Kwack, {Mi Hee} and Song, {Seung Yong} and Choi, {Joon Seok} and Park, {Sang Gyu} and Tacghee Yi and Lee, {Hyun Joo} and Kim, {Dae Duk} and Seo, {Hyun Min} and Song, {Sun U.} and Sung, {Jong Hyuk}",
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Kim, JH, Kim, WK, Sung, YK, Kwack, MH, Song, SY, Choi, JS, Park, SG, Yi, T, Lee, HJ, Kim, DD, Seo, HM, Song, SU & Sung, JH 2014, '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, pp. 1364-1376. https://doi.org/10.1089/scd.2013.0460

The molecular mechanism underlying the proliferating and preconditioning effect of vitamin C on adipose-derived stem cells. / Kim, Ji Hye; Kim, Wang Kyun; Sung, Young Kwan; Kwack, Mi Hee; Song, Seung Yong; Choi, Joon Seok; Park, Sang Gyu; Yi, Tacghee; Lee, Hyun Joo; Kim, Dae Duk; Seo, Hyun Min; Song, Sun U.; Sung, Jong Hyuk.

In: Stem Cells and Development, Vol. 23, No. 12, 15.06.2014, p. 1364-1376.

Research output: Contribution to journalArticle

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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

PY - 2014/6/15

Y1 - 2014/6/15

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.

AB - 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.

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