Development of a new eczema‐like reconstructed skin equivalent for testing child atopic dermatitis–relieving cosmetics

Gu, Hongjian; Zhu, Yi; Jia, Tinghan; Li, Xiao; Lu, Yongbo; Kaku, Ken

doi:10.1111/jocd.13069

Cited by 7 publications

(5 citation statements)

References 32 publications

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“…Human skin equivalents have long served as models of human IFE in place of murine skin (Augustin et al, 1997; Bell et al, 1983; El Ghalbzouri et al, 2009; Gu et al, 2020). We have shown that basal cell heterogeneity in our organoids fully mimics in vivo basal cell heterogeneity during homeostasis, with most of the differentiated states also present.…”

Section: Discussionmentioning

confidence: 99%

Single cell transcriptomics of human skin equivalent organoids

Stabell

Wang

Lee

et al. 2022

Preprint

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Several methods for generating human skin equivalent (HSE) organoid cultures are regularly used to study skin biology and test pharmaceuticals, however few studies have thoroughly characterized these systems. To fill this gap, we used single cell-RNA sequencing to compare the cellular states of in vitro HSEs generated from distinct culture methods, HSEs xenografted onto mice, and in vivo epidermis. By combining differential gene expression, pseudotime analyses, splicing kinetics, and spatial localization, we reconstructed HSE keratinocyte differentiation trajectories that recapitulated known in vivo epidermal differentiation pathways and show that HSEs contain many of the major in vivo cellular states. However, HSEs also develop several unique keratinocyte states, an expanded basal stem cell program, and disrupted terminal differentiation. In addition, cell-cell communication modeling showed the presence of EMT-associated signaling pathways not normally active in homeostatic skin and we show that EGF supplementation influences the EMT signature. Lastly, xenografted HSEs at early timepoints post-transplantation significantly rescued many of the observed in vitro deficits, while undergoing a hypoxic response that drove an alternative differentiation lineage. This study highlights the strengths and limitations of organoid cultures and identifies areas for potential innovation.

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Section: Discussionmentioning

confidence: 99%

Single cell transcriptomics of human skin equivalent organoids

Stabell

Wang

Lee

et al. 2022

Preprint

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“…One month after transplantation, that is, when the xenotransplants were fully revascularized and reinnervated, 4,14,15 the xenotransplants were injected intradermally or intravenously with autologous 1 × 10 7 Th2‐polarized PBMCs (isolated from the relevant xenotransplant donor as described before 12 ), after these had been pretreated for 14 days in vitro with different combinations of IL‐4 (200 U/mL) a prototypical type 2 cytokine, 16 IL‐2 (10 U/mL), a key T‐cell expansion and activation factor, 17,18 and lipopolysaccharide (LPS) (Salmonella enterica serotype enteritidis, Merck, 1 μg/mL). LPS was chosen since it is found in the outer membrane of most gram‐negative bacteria known to aggravate human AD, 19,20 can trigger human skin inflammation, 21–23 and induces dermatitis in human skin 22,24,25 . In another set of experiment, 1 month following transplantation, the skin was tape‐striped six times using a 3 M tape (3 M, USA), following by intradermal injection of 1 × 10 7 Th2‐polarized PMBCs.…”

Section: Methodsmentioning

confidence: 99%

“…LPS was chosen since it is found in the outer membrane of most gram-negative bacteria known to aggravate human AD, 19,20 can trigger human skin inflammation, [21][22][23] and induces dermatitis in human skin. 22,24,25 In another set of experiment, 1 month following transplantation, the skin was tape-striped six times using a 3 M tape (3 M, USA), following by intradermal injection of 1 × 10 7 Th2-polarized PMBCs.…”

Section: Ad Lesion Induction In Vivomentioning

confidence: 99%

Autologous Th2‐polarized lymphocytes induce atopic dermatitis lesions in non‐atopic human skin xenotransplants

Keren

Reich

Bertolini

et al. 2023

Allergy

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Background:The key signals that suffice to induce atopic dermatitis (AD) in human skin remain incompletely understood. Also, current mouse models reflect human AD only unsatisfactorily. Therefore, we have asked whether a humanized AD mouse model can be developed that reflects human AD more faithfully and permit to identify key signals that suffice to induce AD lesions in previously healthy human skin in vivo. Methods: Healthy human skin from non-atopic donors was transplanted onto SCID/ beige mice. After xenotransplant reinnervation by mouse sensory nerve fibers had occurred, mixed autologous human Th2 CD4+ and Tc2 CD8+ T cells that had been pretreated in vitro with IL-2, IL-4, and LPS were injected intradermally into the xenotransplants without skin barrier disruption. Results: Injected non-atopic xenotransplants rapidly developed a morphological, functional, and immunological phenocopy of human AD lesions regarding skin barrier defects, immunopathology including intraepidermal eosinophils, mast cell activation, increase of thymic stromal lymphopoietin, eotaxin-1 and type 2 cytokine circuits, and even showed characteristic neuroimmunological abnormalities such as ß2-adrenergic receptor downregulation. The experimentally induced AD lesions in human skin responded to standard AD therapy (topical dexamethasone or tacrolimus; systemic anti-IL-4Rα antibody [dupilumab]), and relapsed when neurogenic skin inflammation was induced by exposing mice to perceived stress. Conclusions: This new animal model uniquely mimics the complexity of human AD and its clinical response to standard therapy and psychoemotional stressors in vivo, and shows that Th2-polarized lymphocytes associated with excessive IL-4Rα-mediated signaling suffice to induce human AD skin lesions, while atopy and epidermal barrier disruption are dispensable.

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“…Recently, 3D skin model has become a novel skin replacement model due to its similar tissue structure and physiological function to the normal skin tissue, which could be able to bridge the gap between in vitro and in vivo experimental models. [48,49] Hence, we further evaluate the effect of grapefruit essential oil on cell viability of the 3D EpiKutis model, the survival rate of the cells at different concentrations after 24 h treatment was first determined by 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, and the cell activity over 75 % was considered as the safe concentration. The concentration of grapefruit or lime essential oil was set at 8 concentration series from high to low.…”

Section: Effects Of Grapefruit Essential Oil On the 3d Epikutis Modelmentioning

confidence: 99%

Protective Effects of Grapefruit Essential Oil againstStaphylococcus Aureus‐Induced Inflammation and Cell Damage in Human Epidermal Keratinocytes

Zhang

Hua

Zhu³

et al. 2022

Chemistry & Biodiversity

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Staphylococcus aureus (S. aureus) is a common skin pathogenic bacterium, over‐colonization can induce skin infections, while its metabolites can also produce irritation to the skin, often accompanied by eczema dermatitis, specific dermatitis and other skin diseases. Grapefruit essential oil is extracted from the fruit of grapefruit (Citrus maxima (Burm) Merr.), a citrus plant that is rich in flavonoids, phenolic acids and high flavanones. Due to its good odor and biological activity such as anti‐inflammatory, antibacterial, etc., grapefruit essential oil has been widely used as an additive in food. To evaluate the potential application of grapefruit essential oil as raw materials in cosmetics products and health foods, we developed a cell damage model of skin inflammation stimulated by S. aureus metabolites. Compared to that of lime essential oil, an internal control, we found that grapefruit essential oil could significantly promote HaCaT cells proliferation, reduce reactive oxygen species (ROS) production induced by S. aureus metabolites, inhibit the upregulated expression of IL‐1 and COX‐2. In the 3D epidermal model, grapefruit essential oil could recover the decreased LOR and FLG contents caused by S. aureus metabolites. These results demonstrated pharmacological evidence for the anti‐inflammatory effect of grapefruit essential oil, suggesting a potential application of grapefruit essential oil as cosmetic raw materials for repair and alleviating of skin inflammation caused by S. aureus.

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Development of a new eczema‐like reconstructed skin equivalent for testing child atopic dermatitis–relieving cosmetics

Cited by 7 publications

References 32 publications

Single cell transcriptomics of human skin equivalent organoids

Single cell transcriptomics of human skin equivalent organoids

Autologous Th2‐polarized lymphocytes induce atopic dermatitis lesions in non‐atopic human skin xenotransplants

Protective Effects of Grapefruit Essential Oil againstStaphylococcus Aureus‐Induced Inflammation and Cell Damage in Human Epidermal Keratinocytes

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