Tissue Eng Regen Med.  2019 Feb;16(1):93-102. 10.1007/s13770-018-0165-3.

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

Affiliations
  • 1College of Medicine, Dongguk University, 32 Donggukro, Ilsandonggu, Goyang, Gyeonggi 10326, Republic of Korea.
  • 2Department of Biostatistics, Dongguk University, 32 Donggukro, Ilsandonggu, Goyang, Gyeonggi 10326, Republic of Korea.
  • 3College of Korean Medicine, Dongguk University, 123 Dongdaero, Gyeongju, Gyeongsangbuk 38066, Republic of Korea.
  • 4Department of Agricultural Biotechnology, Seoul National University, 1 Gwanak ro, Gwanakgu, Seoul 08826, Republic of Korea.
  • 5Research Institute of Agriculture and Life Sciences, Seoul National University, 1 Gwanakro, Gwanakgu, Seoul 08826, Republic of Korea. ahnji@snu.ac.kr
  • 6Biomedical Research Institute, Seoul National University Hospital, 103 Daehakro, Jongnogu, Seoul 03080, Republic of Korea. leeunju@snu.ac.kr

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 hEMSCs.
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.

Keyword

hE-MSCs; Skin psoriasis; Immune modulation; Psoriasis

MeSH Terms

Animals
Cytokines
Embryonic Stem Cells
Humans*
Lymphocytes
Mesenchymal Stromal Cells*
Mice
Psoriasis*
Skin Diseases
Skin*
Splenomegaly
Tissue Donors
Cytokines
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