Adipose-derived stem cells decolonize skin Staphylococcus aureus by enhancing phagocytic activity of peripheral blood mononuclear cells in the atopic rats
Jaehee Lee1, Leejin Park2, Hyeyoung Kim1, Bong-il Rho2, Rafael Taeho Han1, Sewon Kim3, Hee Jin Kim4, Heung Sik Na1,*, and Seung Keun Back5,*
1Neuroscience Research Institute and Department of Physiology, Korea University College of Medicine, Seoul 02841, 2Glovi Plastic Surgery, Seoul 06031, 3Department of Microbiology, Korea University College of Medicine, Seoul 02841, 4Division of Biological Science and Technology, Science and Technology College, Yonsei University Mirae Campus, Wonju 26493, 5Department of Biomedical Laboratory Science, College of Medical Science, Konyang University, Daejeon 35365, Korea
Author contributions: J.L. designed the experiments. J.L. and L.P. performed animal and flow cytometry experiments. H.K., R.T.H., and S.K. performed molecular biological and histological experiments. J.L. and L.P. contributed to analyses of data. B.I.R. and H.J.K. reviewed the manuscript. J.L. and S.K.B. wrote the manuscript. H.S.N. and S.K.B. supervised the study.
Received: May 9, 2022; Revised: June 16, 2022; Accepted: June 16, 2022
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Staphylococcus aureus (S. aureus) is known to induce apoptosis of host immune cells and impair phagocytic clearance, thereby being pivotal in the pathogenesis of atopic dermatitis (AD). Adipose-derived stem cells (ASCs) exert therapeutic effects against inflammatory and immune diseases. In the present study, we investigated whether systemic administration of ASCs restores the phagocytic activity of peripheral blood mononuclear cells (PBMCs) and decolonizes cutaneous S. aureus under AD conditions. AD was induced by injecting capsaicin into neonatal rat pups. ASCs were extracted from the subcutaneous adipose tissues of naïve rats and administered to AD rats once a week for a month. Systemic administration of ASCs ameliorated AD-like symptoms, such as dermatitis scores, serum IgE, IFN-γ+/IL-4+ cell ratio, and skin colonization by S. aureus in AD rats. Increased FasL mRNA and annexin V+/7-AAD+ cells in the PBMCs obtained from AD rats were drastically reversed when co-cultured with ASCs. In contrast, both PBMCs and CD163+ cells bearing fluorescent zymosan particles significantly increased in AD rats treated with ASCs. Additionally, the administration of ASCs led to an increase in the mRNA levels of antimicrobial peptides, such as cathelicidin and β-defensin, in the skin of AD rats. Our results demonstrate that systemic administration of ASCs led to decolonization of S. aureus by attenuating apoptosis of immune cells in addition to restoring phagocytic activity. This contributes to the improvement of skin conditions in AD rats. Therefore, administration of ASCs may be helpful in the treatment of patients with intractable AD.