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Human Embryonic Stem Cells-Derived Mesenchymal Stem Cells Reduce the Symptom of Psoriasis in Imiquimod-Induced Skin Model

Tissue Engineering and Regenerative Medicine volume 16, pages 93–102 (2019)Cite this article

Abstract

Background:

Mesenchymal stem cells (MSCs) can be used for a wide range of therapeutic applications because of not only their differentiation potential but also their ability to secrete bioactive factors. Recently, several studies have suggested the use of human embryonic stem cell-derived MSCs (hE-MSCs) as an alternative for regenerative cellular therapy due to mass production of MSCs from a single donor.

Methods:

We generated hE-MSCs from embryonic stem cell lines, SNUhES3, and analyzed immune properties of these cells. Also, we evaluated the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease.

Results:

The cell showed the suppression of immunity associated with allogenic peripheral blood mononuclear cells in mixed lymphocyte response assay. We also detected that cytokines and growth factor related to the immune response were secreted from these cells. To assessed the in-vivo therapeutic potential of hE-MSCs in immune-mediated inflammatory skin disease, we used imiquimod (IMQ)-induced skin psoriasis mouse model. The score of clinical skin was significantly reduced in the hE-MSCs treated group compared with control IMQ group. In histological analysis, the IMQ-induced epidermal thickness was significantly decreased by hE-MSCs treatment. It was correlated with splenomegaly induced by IMQ which was also improved in the hE-MSCs. Moreover, IMQ-induced inflammatory cytokines; Th1 cytokines (TNF-α, IFN-α, IFN-γ,and IL-27) and Th17 cytokines (IL-17A and IL-23), in the serum and skin showed marked inhibition by hE-MSCs.

Conclusion:

These results suggested that hE-MSCs have a potency of immune modulation in psoriasis, which might be the key factor for the improved psoriasis.

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Acknowledgements

This work was supported by National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP) (No. 2015R1C1A2A01055746) and supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A1B03934099), Republic of Korea.

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Authors and Affiliations

  1. College of Medicine, Dongguk University, 32 Donggukro, Ilsandonggu, Goyang, Gyeonggi, 10326, Republic of Korea

    Chang-Hyun Kim

  2. Department of Biostatistics, Dongguk University, 32 Donggukro, Ilsandonggu, Goyang, Gyeonggi, 10326, Republic of Korea

    Chi-Yeon Lim

  3. College of Korean Medicine, Dongguk University, 123 Dongdaero, Gyeongju, Gyeongsangbuk, 38066, Republic of Korea

    Ju-Hee Lee

  4. Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak ro, Gwanakgu, Seoul, 08826, Republic of Korea

    Keun Cheon Kim

  5. Research Institute of Agriculture and Life Sciences, Seoul National University, 1 Gwanakro, Gwanakgu, Seoul, 08826, Republic of Korea

    Ji Yeon Ahn

  6. Biomedical Research Institute, Seoul National University Hospital, 103 Daehakro, Jongnogu, Seoul, 03080, Republic of Korea

    Eun Ju Lee

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  1. Chang-Hyun Kim
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Correspondence to Ji Yeon Ahn or Eun Ju Lee.

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The authors have no financial conflicts of interest.

Ethical statement

The study protocol was approved by the institutional review board of Seoul National University Hospital (IRB No. H-1410-093-619). The animal studies were performed after receiving approval of the Institutional Animal Care and Use Committee (IACUC) in Dongguk University Hospital (IACUC approval No. 201606150).

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Kim, CH., Lim, CY., Lee, JH. et al. Human Embryonic Stem Cells-Derived Mesenchymal Stem Cells Reduce the Symptom of Psoriasis in Imiquimod-Induced Skin Model. Tissue Eng Regen Med 16, 93–102 (2019). https://doi.org/10.1007/s13770-018-0165-3

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  • DOI: https://doi.org/10.1007/s13770-018-0165-3

Keywords

  • hE-MSCs
  • Skin psoriasis
  • Immune modulation
  • Psoriasis