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

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
WenDi Fei ◽  
JunLin Wu ◽  
MengDie Gao ◽  
Qian Wang ◽  
Ya Yu Zhao ◽  
...  
Keyword(s):  
Wound Healing ◽  
Atopic Dermatitis ◽  
Stem Cell ◽  
Skin Diseases ◽  
Quantitative Polymerase Chain Reaction ◽  
Inflammatory Factors ◽  
Inflammatory Skin Diseases ◽  
Cell Injection ◽  
Muse Cells

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.

scholarly journals Therapeutic Effects of Fermented Flax Seed Oil on NC/Nga Mice with Atopic Dermatitis-Like Skin Lesions

2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
Joonhyoung Yang ◽  
Sangyeon Min ◽  
Seungug Hong
Keyword(s):  
Atopic Dermatitis ◽  
Seed Oil ◽  
Skin Diseases ◽  
Receptor Expression ◽  
Raw 264.7 Cells ◽  
Therapeutic Effects ◽  
Flax Seed ◽  
Inflammatory Skin Diseases

Background. Atopic Dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Objective. This experiment aimed to study the effects of Fermented Flax Seed Oil (FFSO) on symptoms such as redness, eczema, and pruritus induced by AD. Materials and Methods. AD-induced NC/Nga mice were used to observe the immunological and therapeutic effects of FFSO on skin in vivo. Raw 264.7 cells were used to investigate the effects of FFSO in cells. Fc receptor expression and concentration of beta-hexosaminidase were measured. Nitric oxide assay, Western blotting, real-time PCR, image analysis, and statistical analysis were performed in vitro. Results. In the immunohistochemical results, p-ERK 1/2 expression decreased, fibrogenesis strongly increased, and distribution reduction is observed. Distribution of IL-4-positive cells in the corium near the basal portion of the epithelium in the AT group was reduced. FFSO treatment reduced the number of cells showing NF-κB p65 and iNOS expression. The level of LXR in the AT group was higher than that in the AE group, and elevation of PKC expression was significantly reduced by FFSO treatment. Conclusion. FFSO could alleviate symptoms of AD such as epithelial damage, redness, swelling, and pruritus.

scholarly journals Effect of Neferine on DNCB-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice

2021 ◽  
Vol 22 (15) ◽  
pp. 8237
Author(s):  
Chung-Chi Yang ◽  
Yen-Ling Hung ◽  
Wen-Chin Ko ◽  
Yi-Ju Tsai ◽  
Jia-Feng Chang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Transepidermal Water Loss ◽  
Hacat Cells ◽  
Inflammatory Skin Diseases ◽  
Inflammatory Skin

Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.

scholarly journals Radiofrequency Irradiation Attenuates High-Mobility Group Box 1 and Toll-like Receptor Activation in Ultraviolet B–Induced Skin Inflammation

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1297
Author(s):  
Hyoung Moon Kim ◽  
Seyeon Oh ◽  
Jung Hyun Yoon ◽  
Donghwan Kang ◽  
Myeongjoo Son ◽  
...  
Keyword(s):  
Skin Diseases ◽  
High Mobility ◽  
Skin Inflammation ◽  
Receptor Activation ◽  
Ultraviolet B ◽  
High Mobility Group ◽  
Inflammatory Factors ◽  
Inflammatory Skin Diseases ◽  
Inflammatory Molecules

Ultraviolet B (UVB) exposure activates various inflammatory molecules of keratinocytes in the epidermis layer. Such UVB-mediated skin inflammation leaves post-inflammatory hyperpigmentation (PIH). Reports show a close relationship between PIH and high-mobility group box 1 (HMGB1) and its receptors. General clinical treatments of PIH, such as oral medication and laser treatment, have reported side effects. Recent studies reported the effects of radiofrequency (RF) irradiation on restoring dermal collagen, modulating the dermal vasculature, and thickening the basement membrane. To validate how RF regulates the inflammatory molecules from UVB-irradiated keratinocytes, we used UVB-radiated keratinocytes and macrophages, as well as animal skin. In addition, we examined two cases of RF-irradiated skin inflammatory diseases. We validated the effects of RF irradiation on keratinocytes by measuring expression levels of HMGB1, Toll-like receptors (TLRs), and other inflammatory factors. The results show that the RF modulates UVB-radiated keratinocytes to secrete fewer inflammatory factors and also modulates the expression of macrophages from HMGB1, TLRs, and inflammatory factors. RF irradiation could alleviate inflammatory skin diseases in patients. RF irradiation can regulate the macrophage indirectly through modulating the keratinocyte and inflammatory molecules of macrophages reduced in vitro and in vivo. Although the study is limited by the low number of cases, it demonstrates that RF irradiation can regulate skin inflammation in patients.

scholarly journals Saponin from Periploca forrestii Schltr Mitigates Oxazolone-Induced Atopic Dermatitis via Modulating Macrophage Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Luting Zeng ◽  
Yingqin Liu ◽  
Congcong Xing ◽  
Yijie Huang ◽  
Xin Sun ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Macrophage Activation ◽  
Skin Diseases ◽  
Nuclear Translocation ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Mouse Bone Marrow ◽  
Inflammatory Skin Diseases ◽  
M1 Macrophage

Atopic dermatitis (AD) is a relapsing, acute, and chronic skin disease featured by intractable itching, eczematous skin. Conventional therapies based on immunosuppression such as corticosteroids are associated with multiple adverse reactions. Periploca forrestii Schltr saponin (PFS) was shown to potently inhibit murine arthritis by protecting bone and cartilage injury and suppressing NF-κB activation. However, its therapeutic effect on oxazolone-induced atopic dermatitis (AD) and the underlying mechanisms on macrophage are still unclear. The AD-like dermatitis was induced by repeated oxazolone challenge to the skin of BALB/c mice in vivo. Blood and ears were biochemically or histologically processed. RT-PCR, western blotting, and ELISA were conducted to evaluate the expression of macrophage factors. Mouse bone marrow-derived macrophages (BMDMs) stimulated with lipopolysaccharide (LPS) were used as a model in vitro. PFS treatment inhibited AD-like dermatitis development. PFS downregulated epidermis thickness and cell infiltration, with histological analysis of the skin lesion. PFS alleviated plasma immunoglobulin (Ig) E, IgG2a, and IgG1 levels. PFS downregulated the expression of M1 macrophage factors, tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, monocyte chemotactic protein-1 (MCP-1), and nitric oxide synthase2 (NOS2), and M2 macrophage factors, IL-4, arginase1 (Arg1) and CD163 in AD-like skin, which were confirmed by western blot and ELISA analysis. In addition, PFS inhibited LPS-induced macrophage polarization via the inhibition of the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and nuclear translocation of NF-κB p65. These results suggest that PFS exerted an antidermatitis effect against oxazolone by modulating macrophage activation. PFS administration might be useful in the treatment of AD and inflammatory skin diseases.

scholarly journals Immune response in atopic dermatitis: main pathogenetic mechanisms and stage-dependent correlations with age in regard to dermatological and non-dermatological systemic processes

2021 ◽  
Vol 23 (2) ◽  
pp. 237-244
Author(s):  
M. B. Drozhdina ◽  
E. V. Suslova
Keyword(s):  
Immune Response ◽  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Clinical Manifestations ◽  
Inflammatory Cells ◽  
Interferon Γ ◽  
Lymphoid Cells ◽  
Keratinocyte Differentiation ◽  
Inflammatory Factors ◽  
Inflammatory Skin Diseases

Atopic dermatitis is one of the most common chronic inflammatory skin diseases caused by both terminal defects in keratinocyte differentiation, and pronounced type 2 immune responses. Atopic dermatitis is a fairly heterogenous disease, depending on the age subtype caused by activation of the Th22, Th17/IL-23 and Th1 cytokine pathway. Clinical studies using classical and targeted therapies have helped to determine contribution of various immune axes to the disease phenotype.We present the modern activation theory mediated by Th2 reactions, due to congenital lymphoid cells of the 2nd group. Correlations between immune response in acute (IL-4, IL-5, IL-13, IL-31, CCL18, IL-22, S100A proteins) and chronic (IFNγ, CXCL9, and CXCL10) manifestations of atopic dermatitis are described. The theory of relationship between clinical manifestations and overexpression of some cytokines (IL-4, IL-13) is discussed. The correlation was shown between peripheral blood phenotype in atopic dermatitis of early childhood and in adult patients and individual production of serum biomarkers. In addition to excess Th17 production, early onset of atopic dermatitis in children correlated with elevated levels of antimicrobial peptides, which may serve as a signaling marker that triggers the disease. The article provides information about relationship between atopic dermatitis and other systemic non-allergic processes and diseases (psoriasis, atherosclerosis, cardiovascular diseases, obesity). Despite different polarity of T cells in atopic dermatitis and psoriasis, and different groups of cytokines produced in these diseases. Psoriasis is most of all due to Th17 associated with activation of IL-17, whereas atopic dermatitis is a consequence of Th2 dominance and associated excessive production of IL-4 and IL-13. The both diseases show activation of Th1 and Th22 with increased production of interferon-γ and IL-22, respectively. The article also concerns an interesting hypothesis on effects of the TWEAK protein upon clinical course of atopic dermatitis and psoriasis. In response to increased TWEAK activity, keratinocytes and skin fibroblasts produce a number of chemoattractant and pro-inflammatory factors commonly found in atopic dermatitis and psoriasis, in particular IL-13 and IL-17. TWEAK is not a single etiological factor for atopic dermatitis or psoriasis, but it causes the production of chemokines that promote chemotaxis of pathogenic inflammatory cells into the skin. With further studies of this pathogenetic factor, it will be possible to synthesize a new targeted drug for the treatment of atopic dermatitis and psoriasis. 

scholarly journals Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses

2021 ◽  
Vol 22 (4) ◽  
pp. 1553
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Jungmin Jeon ◽  
Yun Hoo Park ◽  
Tae-Cheol Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mast Cells ◽  
Immune Responses ◽  
Chromatin Remodeling ◽  
Skin Diseases ◽  
Immunoglobulin E ◽  
Critical Role ◽  
Interleukin 4 ◽  
Inflammatory Skin Diseases ◽  
Immune Disorder

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.

scholarly journals Extracellular matrix derived peptides and mesenchymal stem cell motility

2021 ◽  
Author(s):  
◽  
Sandi Grainne Dempsey
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Motility ◽  
Cell Attachment ◽  
Mass Spectrometry Analysis ◽  
And Migration ◽  
Proliferation And Migration

<p>Biomaterials derived from decellularised extracellular matrices have shown promise as tools in tissue regeneration and wound healing. Such materials display biocompatibility as well as inherent bioactivity, promoting constructive remodelling in healing tissues. In this study, the bioactivity of ovine forestomach matrix (a decellularised extracellular matrix biomaterial) is assessed based on its ability to affect the proliferation and migration of wound healing cells.  This material supported cell attachment and proliferation, but did not allow cell infiltration in vitro. Enzymatic digestion of the material rendered soluble components that were able to induce proliferation and migration of some cell types. Cell-mediated processing of the material generated a protein or proteins with chemotactic activity for mesenchymal stem cells in vitro. Mass spectrometry analysis indicated the bioactive component consisted of the proteoglycan decorin, or fragments thereof. Decorin has not previously been shown to induce mesenchymal stem cell motility, and these findings may add to what is known about decorin and its role in constructive remodelling. Furthermore, this cell-mediated approach for ECM breakdown could lead to the discovery of other bioactive peptides involved in ECM remodelling and wound healing.</p>

scholarly journals Itch in Atopic Dermatitis – What Is New?

2021 ◽  
Vol 8 ◽  
Author(s):  
Franz J. Legat
Keyword(s):  
Atopic Dermatitis ◽  
Intracellular Signaling ◽  
Sleep Disturbances ◽  
Skin Diseases ◽  
Immunosuppressive Agents ◽  
Calcineurin Inhibitors ◽  
Inflammatory Skin Diseases ◽  
New Era ◽  
Short And Long Term ◽  
Chronic Pruritus

Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.

Abstract 1767: Feasibility of In Vivo Cardiac Stem Cell Tracking, by SPECT and PET Imaging, Using the Sodium-iodide Symporter as Reporter Gene

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
John Terrovitis ◽  
Keng Fai Kwok ◽  
Riikka Läutamaki ◽  
James M Engles ◽  
Andreas S Barth ◽  
...  
Keyword(s):  
Stem Cell ◽  
Reporter Gene ◽  
Cell Tracking ◽  
Ex Vivo ◽  
Small Animal ◽  
Cell Labeling ◽  
Sodium Iodide Symporter ◽  
Cell Injection

Background. Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo . Aim. To develop a reporter gene that permits in vivo stem cell labeling. We examined the sodium-iodide symporter (NIS), a protein that is not expressed in the heart, but promotes cellular uptake of 99m Tc or 124 I, thus permitting cell tracking by SPECT or PET imaging, respectively. Methods. The human NIS gene ( h NIS) was expressed in rat cardiac derived stem cells (rCDCs) using lentivirus driven by the CAG or CMV promoter. NIS function in transduced cells was confirmed by in vitro 99m Tc uptake. Eleven rats were injected with 1 or 2 million rCDCs intramyocardially immediately after LAD ligation; 6 with CMV-NIS and 5 with CAG-NIS cells. Dual isotope SPECT imaging was performed on a small animal SPECT/CT system, using 99m Tc for cell detection and 201 Tl for myocardial delineation, 24 hrs after cell injection. PET was performed on a small animal PET scanner using 124 I for cell tracking and 13 NH 3 for myocardial delineation, 48hrs after cell injection. Contrast Ratio (CR) was defined as [(signal in the cells)-(signal in blood pool)]/signal in blood pool. High resolution ex vivo SPECT scans of explanted hearts (n=3) were obtained to confirm that in vivo signal was derived from the cell injection site. The presence of h NIS mRNA was confirmed in injected hearts after animal sacrifice (n=2), by real-time RT-PCR. Results. NIS expression in rCDCs did not affect cell viability/proliferation (p=0.718, ctr vs NIS). In vitro 99m Tc uptake was 6.0±0.9% vs 0.07±0.05, without and with perchlorate (specific NIS blocker), respectively. NIS-transduced rCDCs were easily visualized as spots of 99m Tc or 124 I uptake within a perfusion deficit in the SPECT and PET images. CR was considerably higher when cells were transduced by the CMV-NIS virus in comparison to the CAG-NIS virus (70±40% vs 28±29%, p=0.085). Ex vivo small animal SPECT imaging confirmed that in vivo 99m Tc signals were localized to the injection sites. PCR confirmed the presence of h NIS mRNA in injected hearts. Conclusion. NIS expression allows non invasive in vivo stem cell tracking in the myocardium, using both SPECT and PET. This reporter gene has great potential for translation in future clinical applications.

scholarly journals Isolation and Characterization of a Human Fetal Mesenchymal Stem Cell Population: Exploring the Potential for Cell Banking in Wound Healing Therapies

2019 ◽  
Vol 28 (11) ◽  
pp. 1404-1419
Author(s):  
Roger Esteban-Vives ◽  
Jenny Ziembicki ◽  
Myung Sun Choi ◽  
R. L. Thompson ◽  
Eva Schmelzer ◽  
...  
Keyword(s):  
Wound Healing ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Dermal Fibroblasts ◽  
Stem Cell Population ◽  
Differentiation Potential ◽  
Isolation And Characterization ◽  
Cell Banking ◽  
Lineage Stability

Various cell-based therapies are in development to address chronic and acute skin wound healing, for example for burns and trauma patients. An off-the-shelf source of allogeneic dermal cells could be beneficial for innovative therapies accelerating the healing in extensive wounds where the availability of a patient’s own cells is limited. Human fetal-derived dermal fibroblasts (hFDFs) show high in vitro division rates, exhibit low immunological rejection properties, and present scarless wound healing in the fetus, and previous studies on human fetal tissue-derived cell therapies have shown promising results on tissue repair. However, little is known about cell lineage stability and cell differentiation during the cell expansion process, required for any potential therapeutic use. We describe an isolation method, characterize a population, and investigate its potential for cell banking and thus suitability as a potential product for cell grafting therapies. Our results show hFDFs and a bone marrow-derived mesenchymal stem cell (BM-MSC) line shared identification markers and in vitro multilineage differentiation potential into osteogenic, chondrogenic, and adipogenic lineages. The hFDF population exhibited similar cell characteristics as BM-MSCs while producing lower pro-inflammatory cytokine IL-6 levels and higher levels of the wound healing factor hepatocyte growth factor. We demonstrate in vitro differentiation of hFDFs, which may be a problem in maintaining long-term lineage stability, potentially limiting their use for cell banking and therapy development.

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