Abstract
Mesenchymal stem cells (MSCs) are a promising tool for treating immune disorders. However, the immunomodulatory effects of canine MSCs compared with other commercialized biologics for treating immune disorders have not been well studied. In this study we investigated the characteristics and immunomodulatory effects of canine amnion membrane (cAM)-MSCs. We examined gene expression of immune modulation and T lymphocytes from activated canine peripheral blood mononuclear cell (PBMC) proliferation. As a result, we confirmed that cAM-MSCs upregulated immune modulation genes (TGF-β1, IDO1 and PTGES2) and suppressed the proliferation capacity of T cells. Moreover, we confirmed the therapeutic effect of cAM-MSCs compared with oclacitinib (OCL), the most commonly used Janus kinase (JAK) inhibitor, as a treatment for canine atopic dermatitis (AD) using a mouse AD model. As a result, we confirmed that cAM-MSCs with PBS treatment groups (passage 4, 6 and 8) compared with PBS only (PBS) though scores of dermatologic signs, tissue pathologic changes and inflammatory cytokines were significantly reduced. In particular, cAM-MSCs were more effective than OCL in the recovery of wound dysfunction, regulation of mast cell activity and expression level of immune modulation protein. Interestingly, subcutaneous injection of cAM-MSCs induced weight recovery, but oral administration of oclacitinib induced weight loss as a side effect. In conclusion, this study suggests that cAM-MSCs can be developed as a safe canine treatment for atopic dermatitis without side effects through effective regeneration and immunomodulation.
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Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- AD:
-
Atopic dermatitis
- cAM:
-
Canine amniotic membrane
- cAM-MSCs:
-
Canine amnion membrane-derived MSCs
- CCR7:
-
C-C chemokine receptor type 7
- conA:
-
Concanavalin A
- CPDL:
-
Cumulative population doubling level
- CTL:
-
Control
- DMSO:
-
Dimethyl Sulfoxide
- GVHD:
-
Graft-Versus-Host Disease
- IDO1:
-
Indoleamine 2,3-dioxygenase 1
- IL-6:
-
Interleukin-6
- IL-17:
-
Interleukin-17
- JAK:
-
Janus kinase
- n.s.:
-
Not statistically significant versus Static
- MLR:
-
Mixed Lymphocyte Reaction
- OCL:
-
Oclacitinib
- PBS:
-
Phosphate buffered saline
- PBMC:
-
Peripheral blood mononuclear cells
- PGE2:
-
Prostaglandin E2
- PFA:
-
Para formaldehyde
- PBST:
-
PBS comprising Triton-X 100
- SBS:
-
Sick Building syndrome
- TGF-β1:
-
Transforming Growth Factor-β1
- Treg cell:
-
Regulartory Tcell
- Th2 cell:
-
T helper 2 cell
- Th17 cell:
-
T helper 17 cell
- TNF-α:
-
Tumor necrosis factor-α
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This study has received research support from Seoul National University Veterinary Medical Teaching Hospital and Kangstem biotech.
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M.S.K. designed and performed the majority of experiments and wrote the paper with input from all authors. D.S.K., M.H.H. assisted with the experiments. H.J.K. participated in the animal experiments. S.H.L. and K.-S.K. participated in experimental design and provided advice during the experiment procedure. K.H.R., S.H.L. and K.-S.K. did financial support and final approval of the manuscript. All authors read and approved the final manuscript.
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All animal experimental procedures were approved by the Seoul National University Institutional Animal Care and Use Committee. All experiments using cAM-MSCs were approved by the IRB of the Public Institutional Bioethics Committee designated by the South Korea Ministry of Health and Welfare.
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Kim, M.S., Kong, D., Han, M. et al. Canine amniotic membrane-derived mesenchymal stem cells ameliorate atopic dermatitis through regeneration and immunomodulation. Vet Res Commun 47, 2055–2070 (2023). https://doi.org/10.1007/s11259-023-10155-5
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DOI: https://doi.org/10.1007/s11259-023-10155-5