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.

scholarly journals Assessment of Human Skin Gene Expression by Different Blends of Plant Extracts with Implications to Periorbital Skin Aging

2018 ◽  
Vol 19 (11) ◽  
pp. 3349 ◽  
Author(s):  
Jin Namkoong ◽  
Dale Kern ◽  
Helen Knaggs
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Human Skin ◽  
Barrier Function ◽  
Skin Barrier ◽  
Skin Aging ◽  
Skin Barrier Function ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
And Oxidative Stress

Since the skin is the major protective barrier of the body, it is affected by intrinsic and extrinsic factors. Environmental influences such as ultraviolet (UV) irradiation, pollution or dry/cold air are involved in the generation of radical oxygen species (ROS) and impact skin aging and dermal health. Assessment of human skin gene expression and other biomarkers including epigenetic factors are used to evaluate the biological/molecular activities of key compounds in cosmetic formulas. The objective of this study was to quantify human gene expression when epidermal full-thickness skin equivalents were exposed to: (a) a mixture of betaine, pentylene glycol, Saccharomyces cerevisiae and Rhodiola rosea root extract (BlendE) for antioxidant, skin barrier function and oxidative stress (with hydrogen peroxide challenge); and (b) a mixture of Narcissus tazetta bulb extract and Schisandra chinensis fruit extract (BlendIP) for various biomarkers and microRNA analysis. For BlendE, several antioxidants, protective oxidative stress biomarkers and many skin barrier function parameters were significantly increased. When BlendE was evaluated, the negative impact of the hydrogen peroxide was significantly reduced for the matrix metalloproteinases (MMP 3 and MMP 12), the skin aging and oxidative stress biomarkers, namely FBN2, ANXA1 and HGF. When BlendIP was tested for cell proliferation and dermal structural components to enhance the integrity of the skin around the eyes: 8 growth factors, 7 signaling, 7 structural/barrier function and 7 oxidative stress biomarkers were significantly increased. Finally, when BlendIP was tested via real-time RT-PCR for microRNA expression: miR-146a, miR-22, miR155, miR16 and miR21 were all significantly increased over control levels. Therefore, human skin gene expression studies are important tools to assess active ingredient compounds such as plant extract blends to advance dermal hypotheses toward validating cosmetic formulations with botanical molecules.

IDR‐1018 induces cell proliferation, migration, and reparative gene expression in 2D culture and 3D human skin equivalents

2019 ◽  
Vol 13 (11) ◽  
pp. 2018-2030
Author(s):  
Thuany Alencar‐Silva ◽  
Alessandra Zonari ◽  
Daniel Foyt ◽  
Mylieneth Gang ◽  
Robert Pogue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Human Skin ◽  
Skin Equivalents

scholarly journals Testing the Effectiveness of Curcuma longa Leaf Extract on a Skin Equivalent Using a Pumpless Skin-on-a-Chip Model

2020 ◽  
Vol 21 (11) ◽  
pp. 3898 ◽  
Author(s):  
Kyunghee Kim ◽  
Hye Mi Jeon ◽  
Kyung Chan Choi ◽  
Gun Yong Sung
Keyword(s):  
Drug Testing ◽  
Leaf Extract ◽  
Curcuma Longa ◽  
Microfluidic Channel ◽  
Skin Equivalent ◽  
Skin Barrier Function ◽  
In Vitro Tests ◽  
Functional Responses ◽  
Culture Methods ◽  
Pharmaceutical Industries

The in vitro tests in current research employ simple culture methods that fail to mimic the real human tissue. In this study, we report drug testing with a ‘pumpless skin-on-a-chip’ that mimics the structural and functional responses of human skin. This model is a skin equivalent constituting two layers of the skin, dermis and epidermis, developed using human primary fibroblasts and keratinocytes. Using the gravity flow device system, the medium was rotated at an angle of 15 degrees on both sides so as to circulate through the pumpless skin-on-a-chip microfluidic channel. This pumpless skin-on-a-chip is composed of upper and lower chips, and is manufactured using porous membranes so that medium can be diffused and supplied to the skin equivalent. Drug testing was performed using Curcuma longa leaf extract (CLLE), a natural product cosmetic ingredient, to evaluate the usefulness of the chip and the efficacy of the cosmetic ingredient. It was found that the skin barrier function of the skin epidermis layer is enhanced to exhibit antiaging effects. This result indicates that the pumpless skin-on-a-chip model can be potentially used not only in the cosmetics and pharmaceutical industries but also in clinical applications as an alternative to animal studies.

scholarly journals Pumpless microfluidic platform for drug testing on human skin equivalents

Lab on a Chip ◽  
2015 ◽  
Vol 15 (3) ◽  
pp. 882-888 ◽  
Author(s):  
Hasan Erbil Abaci ◽  
Karl Gledhill ◽  
Zongyou Guo ◽  
Angela M. Christiano ◽  
Michael L. Shuler
Keyword(s):  
Human Skin ◽  
Drug Screening ◽  
Drug Testing ◽  
Microfluidic Platform ◽  
Skin Equivalents ◽  
Human Skin Models

Advances in bio-mimetic in vitro human skin models increase the efficiency of drug screening studies.

scholarly journals Synthetic Retinoid Seletinoid G Improves Skin Barrier Function through Wound Healing and Collagen Realignment in Human Skin Equivalents

2020 ◽  
Vol 21 (9) ◽  
pp. 3198 ◽  
Author(s):  
Eun-Soo Lee ◽  
Yujin Ahn ◽  
Il-Hong Bae ◽  
Daejin Min ◽  
Nok Hyun Park ◽  
...  
Keyword(s):  
Wound Healing ◽  
Human Skin ◽  
Barrier Function ◽  
Second Harmonic ◽  
Skin Barrier ◽  
The Body ◽  
Skin Barrier Function ◽  
Extrinsic Factors ◽  
Impaired Wound Healing ◽  
Skin Equivalents

The outer epidermal skin is a primary barrier that protects the body from extrinsic factors, such as ultraviolet (UV) radiation, chemicals and pollutants. The complete epithelialization of a wound by keratinocytes is essential for restoring the barrier function of the skin. However, age-related alterations predispose the elderly to impaired wound healing. Therefore, wound-healing efficacy could be also considered as a potent function of an anti-aging reagent. Here, we examine the epidermal wound-healing efficacy of the fourth-generation retinoid, seletinoid G, using HaCaT keratinocytes and skin tissues. We found that seletinoid G promoted the proliferation and migration of keratinocytes in scratch assays and time-lapse imaging. It also increased the gene expression levels of several keratinocyte proliferation-regulating factors. In human skin equivalents, seletinoid G accelerated epidermal wound closure, as assessed using optical coherence tomography (OCT) imaging. Moreover, second harmonic generation (SHG) imaging revealed that seletinoid G recovered the reduced dermal collagen deposition seen in ultraviolet B (UVB)-irradiated human skin equivalents. Taken together, these results indicate that seletinoid G protects the skin barrier by accelerating wound healing in the epidermis and by repairing collagen deficiency in the dermis. Thus, seletinoid G could be a potent anti-aging agent for protecting the skin barrier.

scholarly journals Sarcoptes scabiei Mites Modulate Gene Expression in Human Skin Equivalents

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e71143 ◽  
Author(s):  
Marjorie S. Morgan ◽  
Larry G. Arlian ◽  
Michael P. Markey
Keyword(s):  
Gene Expression ◽  
Human Skin ◽  
Sarcoptes Scabiei ◽  
Skin Equivalents

scholarly journals EGFR inhibitors switch keratinocytes from a proliferative to a differentiative phenotype affecting epidermal development and barrier function

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nicolas Joly-Tonetti ◽  
Thomas Ondet ◽  
Mario Monshouwer ◽  
Georgios N. Stamatas
Keyword(s):  
Growth Factor ◽  
Barrier Function ◽  
Kinase Inhibitors ◽  
Treatment Protocol ◽  
Growth Factor Receptor ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Skin Barrier Function ◽  
Epidermal Keratinocytes ◽  
Epidermal Structure

Abstract Background Cutaneous adverse drug reactions (CADR) associated with oncology therapy involve 45–100% of patients receiving kinase inhibitors. Such adverse reactions may include skin inflammation, infection, pruritus and dryness, symptoms that can significantly affect the patient’s quality of life. To prevent severe skin damages dose adjustment or drug discontinuation is often required, interfering with the prescribed oncology treatment protocol. This is particularly the case of Epidermal Growth Factor Receptor inhibitors (EGFRi) targeting carcinomas. Since the EGFR pathway is pivotal for epidermal keratinocytes, it is reasonable to hypothesize that EGFRi also affect these cells and therefore interfere with the epidermal structure formation and skin barrier function. Methods To test this hypothesis, the effects of EGFRi and Vascular Endothelial Growth Factor Receptor inhibitors (VEGFRi) at therapeutically relevant concentrations (3, 10, 30, 100 nM) were assessed on proliferation and differentiation markers of human keratinocytes in a novel 3D micro-epidermis tissue culture model. Results EGFRi directly affect basal keratinocyte growth, leading to tissue size reduction and switching keratinocytes from a proliferative to a differentiative phenotype, as evidenced by decreased Ki67 staining and increased filaggrin, desmoglein-1 and involucrin expression compared to control. These effects lead to skin barrier impairment, which can be observed in a reconstructed human epidermis model showing a decrease in trans-epidermal water loss rates. On the other hand, pan-kinase inhibitors mainly targeting VEGFR barely affect keratinocyte differentiation and rather promote a proliferative phenotype. Conclusions This study contributes to the mechanistic understanding of the clinically observed CADR during therapy with EGFRi. These in vitro results suggest a specific mode of action of EGFRi by directly affecting keratinocyte growth and barrier function.

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 Effects of a complex mixture prepared from agrimonia, houttuynia, licorice, peony, and phellodendron on human skin cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyung-Ha Lee ◽  
Jeong Pyo Lee ◽  
Wanil Kim
Keyword(s):  
Human Skin ◽  
Complex Mixture ◽  
Skin Barrier ◽  
Aging Effect ◽  
Human Keratinocytes ◽  
Skin Barrier Function ◽  
Active Ingredients ◽  
Γ Irradiation ◽  
Skin Cells ◽  
Human Skin Cells

AbstractActive ingredients derived from natural sources are widely utilized in many industries. Cosmetic active ingredients are largely derived from various plants. In this study, we examined whether a mixture of plant extracts obtained from agrimonia, houttuynia, licorice, peony, and phellodendron (hereafter AHLPP), which are well-known for their effects on skin, could affect skin barrier function, inflammation, and aging in human skin cells. We also determined whether AHLPP extracts sterilized using γ-irradiation (to avoid preservatives) retained their skin cell regulating activity. The AHLPP mixture could downregulate representative pro-inflammatory cytokines including IL 1-β and IL 7. Procollagen peptide synthesis was also increased by AHLPP treatment along with mRNA upregulation of barrier proteins such as filaggrin and desmoplakin. The AHLPP mixture showed an anti-aging effect by significantly upregulating telomerase activity in human keratinocytes. We further observed TERT upregulation and CDKN1B downregulation, implying a weakening of pro-aging signal transduction. Co-cultivation of a hydrogel polymer containing the AHLPP mixture with human skin cells showed an alteration in skin-significant genes such as FLG, which encodes filaggrin. Thus, the AHLPP mixture with or without γ-irradiation can be utilized for skin protection as it alters the expression of some significant genes in human skin cells.

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