Multilineage-differentiating stress-enduring cells alleviate atopic dermatitis-associated behaviors in mice

Abstract

Background Pruritus is a recurring, long-lasting skin disease with few effective treatments. Many patients have unsatisfactory responses to currently available antipruritic treatments, and effective therapeutics are urgently needed to relieve symptoms. A previous study reported that mesenchymal stem cell (MSC)-mediated immune regulation could be used to treat skin inflammatory diseases. Multilineage-differentiating stress-enduring (Muse) cells are a new type of pluripotent stem cell that may also have the potential to treat inflammatory skin diseases. Methods Muse cells were isolated from human bone marrow-derived MSCs (BMSCs) via the 8-h longterm trypsin incubation (LTT) method. Repeated use of 2,4-dinitrofluorobenzene (DNFB) induced atopic dermatitis (AD) in a mouse model. Immunofluorescence, behavior recording, and image analysis were used to evaluate the therapeutic effect of subcutaneous Muse cell injection. Real-time quantitative polymerase chain reaction (qPCR) was used to measure the expression of inflammatory factors. In vitro, wound healing and cell proliferation experiments were used to examine the effect of Muse cell supernatant on keratinocytes. Results Our results showed that subcutaneous injection of Muse cells after AD model induction significantly alleviated scratching behavior in mice. The evaluation of dermatitis and photos of damaged skin on the back of the neck revealed that Muse cells reduced dermatitis, playing an active role in healing the damaged skin. The activation of spinal glial cells and scratching behavior were also reduced by Muse cell injection. In addition, we also showed that the expression levels of the inflammatory factors interleukin (IL)-6, IL-17α, and IL-33 in both the spinal cord and skin were suppressed by Muse cells. Furthermore, Muse cells not only exerted anti-inflammatory effects on lipopolysaccharide (LPS)-induced human HaCat cells but also promoted wound healing and keratinocyte proliferation. Conclusions In vivo, Muse cells could alleviate scratching symptoms, reduce epidermal inflammation, and promote wound healing. In vitro, Muse cells could also promote the migration and proliferation of keratinocytes. In summary, Muse cells may become a new therapeutic agent for the treatment of AD.

Multilineage-Differentiating Stress-Enduring Cells: A Powerful Tool for Tissue Damage Repair

“…To date, Muse cells have been used in neurological diseases [63,66,[107][108][109][110][111][112], cardiac systemic diseases [39,49,55,75,[113][114][115][116], renal diseases [40,99,117], dermatological diseases [44,78,[118][119][120], liver diseases [29,41,67,101,121], and other diseases to demonstrate their desirable effects in treating and repairing damaged tissues. In these disease models, Muse cells can migrate to the lesion site and spontaneously differentiate into histocompatible cells such as neurons (ectoderm) [43,111,122], cardiomyocytes (mesoderm) [115,123], glomerulocytes (mesoderm) [40,117], vascular endothelial cells (mesoderm) [34,120]and hepatocytes (entoderm) [41,101,121].…”

Multilineage-Differentiating Stress-Enduring Cells (Muse Cells): An Easily Accessible, Pluripotent Stem Cell Niche with Unique and Powerful Properties for Multiple Regenerative Medicine Applications

“…In another study, a mouse model of atopic dermatitis was treated with subcutaneous injection of Muse cells. Muse cells significantly alleviated scratching behavior in mice, reduced dermatitis, and played an active role in healing damaged skin [ 64 ].…”

Endogenous reparative pluripotent Muse cells with a unique immune privilege system: Hint at a new strategy for controlling acute and chronic inflammation

“…In animal models of PHLF, renal injury, pancreatitis, and atopic dermatitis, Muse cells reduced the production of inflammatory cytokines (IL-1B, IL-6, IL-17A, IL-33, TNF) and increased the expression of anti-inflammatory cytokines (IL-10, PGE2, TGF-β, TSG-6) and growth factors (IGF1, VEGFA, VEGFB, VEGFC, VEGFD, EGF, TGFA), contributing to tissue protection and regeneration in the injured organs rather than MSCs ( Uchida et al, 2017b ; Hosoyama et al, 2018 ; Fei et al, 2021 ; Iseki et al, 2021 ; Fukase et al, 2022 ; Furuta et al, 2022 ).…”

“…In animal models of liver damage, chronic kidney disease, and acute myocardial infarction, intravenously injected Muse cells exhibited a statistically meaningful reduction of fibrosis compared with the MSCs or non-Muse MSCs ( Uchida et al, 2017a ; Iseki et al, 2017 ; Yamada et al, 2018 ; Iseki et al, 2021 ). Since the anti-fibrotic effect is mainly required after the acute phase, MSCs and non-Muse MSCs showed limited effectiveness compared to Muse cells since MSCs and non-Muse MSCs do not home to damaged tissue, nor do they remain in the tissue or the body for more than 2 weeks after administration ( Uchida et al, 2017b ; Yamada et al, 2018 ; Fei et al, 2021 ; Iseki et al, 2021 ).…”