scholarly journals 688 Epithelial precursor cell-conditioned media ameliorates UV irradiation-induced extracellular matrix damage in human skin equivalents

2017 ◽  
Vol 137 (10) ◽  
pp. S311
Author(s):  
D. Kim ◽  
H. Kim ◽  
S. Sohn ◽  
A. Kim ◽  
S. Baek ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Human Skin ◽  
Uv Irradiation ◽  
Precursor Cell ◽  
Conditioned Media ◽  
Skin Equivalents ◽  
Matrix Damage

scholarly journals Vascularised human skin equivalents as a novel in vitro model of skin fibrosis and platform for testing of antifibrotic drugs

2019 ◽  
Vol 78 (12) ◽  
pp. 1686-1692 ◽  
Author(s):  
Alexandru-Emil Matei ◽  
Chih-Wei Chen ◽  
Lisa Kiesewetter ◽  
Andrea-Hermina Györfi ◽  
Yi-Nan Li ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Human Skin ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Skin Fibrosis ◽  
Skin Equivalents ◽  
Artificial Environment ◽  
Key Features ◽  
Antifibrotic Drugs

ObjectivesFibrosis is a complex pathophysiological process involving interplay between multiple cell types. Experimental modelling of fibrosis is essential for the understanding of its pathogenesis and for testing of putative antifibrotic drugs. However, most current models employ either phylogenetically distant species or rely on human cells cultured in an artificial environment. Here we evaluated the potential of vascularised in vitro human skin equivalents as a novel model of skin fibrosis and a platform for the evaluation of antifibrotic drugs.MethodsSkin equivalents were assembled on a three-dimensional extracellular matrix by sequential seeding of endothelial cells, fibroblasts and keratinocytes. Fibrotic transformation on exposure to transforming growth factor-β (TGFβ) and response to treatment with nintedanib as an established antifibrotic agent were evaluated by quantitative polymerase chain reaction (qPCR), capillary Western immunoassay, immunostaining and histology.ResultsSkin equivalents perfused at a physiological pressure formed a mature, polarised epidermis, a stratified dermis and a functional vessel system. Exposure of these models to TGFβ recapitulated key features of SSc skin with activation of TGFβ pathways, fibroblast to myofibroblast transition, increased release of collagen and excessive deposition of extracellular matrix. Treatment with the antifibrotic agent nintedanib ameliorated this fibrotic transformation.ConclusionOur data provide evidence that vascularised skin equivalents can replicate key features of fibrotic skin and may serve as a platform for evaluation of antifibrotic drugs in a pathophysiologically relevant human setting.

Neutrophil elastase contributes to extracellular matrix damage induced by chronic low-dose UV irradiation in a hairless mouse photoaging model

2010 ◽  
Vol 60 (3) ◽  
pp. 151-158 ◽  
Author(s):  
Hirotaka Takeuchi ◽  
Takamasa Gomi ◽  
Mayumi Shishido ◽  
Hiroshi Watanabe ◽  
Noriko Suenobu
Keyword(s):  
Extracellular Matrix ◽  
Uv Irradiation ◽  
Neutrophil Elastase ◽  
Low Dose ◽  
Hairless Mouse ◽  
Matrix Damage

Constructing Human Skin Equivalents on Porcine Acellular Peritoneum Extracellular Matrix forIn VitroIrritation Testing

2016 ◽  
Vol 22 (1-2) ◽  
pp. 111-122 ◽  
Author(s):  
Pei-Chin Tsai ◽  
Zheng Zhang ◽  
Charles Florek ◽  
Bozena B. Michniak-Kohn
Keyword(s):  
Extracellular Matrix ◽  
Human Skin ◽  
Skin Equivalents

scholarly journals OP0195 VASCULARIZED THREE-DIMENSIONAL MODELS OF HUMAN SKIN FIBROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 121.2-122
Author(s):  
A. E. Matei ◽  
C. W. Chen ◽  
L. Kiesewetter ◽  
A. H. Györfi ◽  
Y. N. LI ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Human Skin ◽  
Three Dimensional ◽  
Cell Polarization ◽  
Skin Fibrosis ◽  
Matrix Deposition ◽  
Skin Equivalents ◽  
Antifibrotic Drugs

Background:The complex pathophysiological processes that result in fibrotic tissue remodeling in systemic sclerosis involve interplay between multiple cell types (1). Experimental models of fibrosis are essential to provide a conceptual understanding of the pathogenesis of these diseases and to test antifibrotic drugs. Current models of fibrosis have important limitations: thein vivomodels rely on species that are phylogenetically distant, whereas thein vitromodels are oversimplified cultures of a single cell type in an artificial two-dimensional environment of excessive stiffness, which imposes an unphysiological cell polarization (2).Objectives:Here we evaluated the potential use of vascularized, three-dimensionalin vitrohuman skin equivalents as a novel model of skin fibrosis and a platform for the evaluation of antifibrotic drugs.Methods:Skin equivalents were generated by seeding human endothelial cells, fibroblasts and keratinocytes on a decellularized porcine extracellular matrix with perfusable vascular structure. The skin models were cultured for one month in a system that ensured perfusion of the vascular network at physiological pressure. Fibrotic transformation induced by TGFβ and response to nintedanib as an established antifibrotic drug was evaluated by capillary Western immunoassays, qPCR, histology and immunostaining.Results:The vascularized human skin equivalents formed the major skin structures relevant for the pathogenesis of fibrosis: a polarized, fully matured epidermis, a stratified dermis and a perfused vessel system with small capillaries. Exposure to TGFβ led to the fibrotic transformation of the skin equivalents, with activated TGFβ downstream pathways, increased fibroblast-to-myofibroblast transition and excessive deposition of extracellular matrix. Treatment of models exposed to TGFβ with nintedanib (a drug with proven antifibrotic effects) ameliorated the fibrotic transformation of skin equivalents with reduced TGFβ signaling, fibroblast-to-myofibroblast transition and decreased extracellular matrix deposition.Conclusion:Here we describe a novelin vitromodel of skin fibrosis. Our data show that vascularized skin equivalents can reproduce all skin layers affected by fibrosis, that, upon exposure to TGFβ, these models recapitulate key features of fibrotic skin and that these skin models can be used as a platform for evaluation of antifibrotic drugs in a setting with high relevance for human disease.References:[1]Distler JHW, Gyorfi AH, Ramanujam M, Whitfield ML, Konigshoff M, Lafyatis R. Shared and distinct mechanisms of fibrosis. Nature reviews Rheumatology. 2019;15(12):705-30.[2]Garrett SM, Baker Frost D, Feghali-Bostwick C. The mighty fibroblast and its utility in scleroderma research. Journal of scleroderma and related disorders. 2017;2(2):69-134.Disclosure of Interests:Alexandru-Emil Matei: None declared, Chih-Wei Chen: None declared, Lisa Kiesewetter: None declared, Andrea-Hermina Györfi: None declared, Yi-Nan Li: None declared, Thuong Trinh-Minh: None declared, Toin van Kuppevelt: None declared, Jan Hansmann: None declared, Astrid Juengel: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Florian Groeber-Becker: None declared, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim

scholarly journals Mechanical and Immunological Regulation in Wound Healing and Skin Reconstruction

2021 ◽  
Vol 22 (11) ◽  
pp. 5474
Author(s):  
Shun Kimura ◽  
Takashi Tsuji
Keyword(s):  
Tissue Engineering ◽  
Wound Healing ◽  
Human Skin ◽  
Developmental Stages ◽  
Control Mechanisms ◽  
Tissue Remodelling ◽  
Skin Equivalents ◽  
Immunological Interactions ◽  
Stress Signals ◽  
Specific Species

In the past decade, a new frontier in scarless wound healing has arisen because of significant advances in the field of wound healing realised by incorporating emerging concepts from mechanobiology and immunology. The complete integumentary organ system (IOS) regeneration and scarless wound healing mechanism, which occurs in specific species, body sites and developmental stages, clearly shows that mechanical stress signals and immune responses play important roles in determining the wound healing mode. Advances in tissue engineering technology have led to the production of novel human skin equivalents and organoids that reproduce cell–cell interactions with tissue-scale tensional homeostasis, and enable us to evaluate skin tissue morphology, functionality, drug response and wound healing. This breakthrough in tissue engineering has the potential to accelerate the understanding of wound healing control mechanisms through complex mechanobiological and immunological interactions. In this review, we present an overview of recent studies of biomechanical and immunological wound healing and tissue remodelling mechanisms through comparisons of species- and developmental stage-dependent wound healing mechanisms. We also discuss the possibility of elucidating the control mechanism of wound healing involving mechanobiological and immunological interaction by using next-generation human skin equivalents.

scholarly journals Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

2021 ◽  
Vol 22 (4) ◽  
pp. 2160
Author(s):  
Kyunghee Kim ◽  
Jisue Kim ◽  
Hyoungseob Kim ◽  
Gun Yong Sung
Keyword(s):  
Gene Expression ◽  
Human Skin ◽  
Lipoic Acid ◽  
Drug Testing ◽  
Structural Integrity ◽  
Microfluidic Channel ◽  
Skin Barrier Function ◽  
Animal Testing ◽  
Epidermal Structure ◽  
Skin Equivalents

Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.

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