Human skin equivalents cultured under hypoxia display enhanced epidermal morphogenesis and lipid barrier formation

Mieremet, Arnout; García, Adela Vázquez; Boiten, Walter; Dijk, Rianne van; Gooris, Gert S.; Bouwstra, Joke A.; Ghalbzouri, Abdoelwaheb El

doi:10.1038/s41598-019-44204-4

Cited by 36 publications

(34 citation statements)

References 64 publications

(76 reference statements)

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“…Declaration of Helsinki principles is followed during the obtainment of primary cells from surplus female adult mama skin tissue, as stated earlier [21, 29]. Isolation of primary cells from the dermis and epidermis and cell culturing was performed as described before [12, 51].…”

Section: Methodsmentioning

confidence: 99%

Unravelling effects of relative humidity on lipid barrier formation in human skin equivalents

et al. 2019

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Relative humidity (RH) levels vary continuously in vivo, although during in vitro generation of three-dimensional human skin equivalents (HSEs) these remain high (90–95%) to prevent evaporation of the cell-culture medium. However, skin functionality is directly influenced by environmental RH. As the barrier formation in HSEs is different, there is a need to better understand the role of cell-culture conditions during the generation of HSEs. In this study, we aim to investigate the effects of RH on epidermal morphogenesis and lipid barrier formation in HSEs. Therefore, two types of HSEs were developed at 90% or at 60% RH. Assessments were performed to determine epidermal morphogenesis by immunohistochemical analyses, ceramide composition by lipidomic analysis, and lipid organization by Fourier transform infrared spectroscopy and small-angle X-ray diffraction. We show that reduction of RH mainly affected the uppermost viable epidermal layers in the HSEs, including an enlargement of the granular cells and induction of epidermal cell activation. Neither the composition nor the organization of the lipids in the intercorneocyte space were substantially altered at reduced RH. In addition, lipid processing from glucosylceramides to ceramides was not affected by reduced RH in HSEs as shown by enzyme expression, enzyme activity, and substrate-to-product ratio. Our results demonstrate that RH directly influences epidermal morphogenesis, albeit the in vitro lipid barrier formation is comparable at 90% and 60% RH.Electronic supplementary materialThe online version of this article (10.1007/s00403-019-01948-3) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Unravelling effects of relative humidity on lipid barrier formation in human skin equivalents

et al. 2019

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“…However, one must keep in mind that 3D skin models possess weaker barrier properties compared to the native skin. More advanced and relevant 3D skin models are developed that include immune cells, melanocytes, sebocytes, and endothelial cells, stimuli for lipid synthesis [261], and cultivation conditions closer to the real-life situation [262]; hence a complete immune system [263], vascularization [264], and barrier properties similar to human skin are the main elements that current models are lacking [265]. Skin surface lipids (e.g., sebum) were not considered to date in 3D skin models utilized for PMtesting.…”

Section: Future Directionsmentioning

confidence: 99%

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Dijkhoff¹,

Drašler²,

Karakoçak³

et al. 2020

Part Fibre Toxicol

122

116

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Background: Air pollution is killing close to 5 million people a year, and harming billions more. Air pollution levels remain extremely high in many parts of the world, and air pollution-associated premature deaths have been reported for urbanized areas, particularly linked to the presence of airborne nano-sized and ultrafine particles. Main text: To date, most of the research studies did focus on the adverse effects of air pollution on the human cardiovascular and respiratory systems. Although the skin is in direct contact with air pollutants, their damaging effects on the skin are still under investigation. Epidemiological data suggested a correlation between exposure to air pollutants and aggravation of symptoms of chronic immunological skin diseases. In this study, a systematic literature review was conducted to understand the current knowledge on the effects of airborne particulate matter on human skin. It aims at providing a deeper understanding of the interactions between air pollutants and skin to further assess their potential risks for human health. Conclusion: Particulate matter was shown to induce a skin barrier dysfunction and provoke the formation of reactive oxygen species through direct and indirect mechanisms, leading to oxidative stress and induced activation of the inflammatory cascade in human skin. Moreover, a positive correlation was reported between extrinsic aging and atopic eczema relative risk with increasing particulate matter exposure.

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“…Considerable efforts have been conducted to optimise oxygen levels of cultured cells, in order to control (stem) cell fate 91 and promote ECM synthesis and deposition for the desired tissue engineering application (Table 7 ), such as skin 92 , cartilage 93 , 94 , bone 95 , 96 , tendon 97 , 98 and heart 89 . For example, low oxygen tension (5% O 2 ) has been shown to retain undifferentiated and multipotent status of MSC cultures 99 , 100 .…”

Section: Limitations and Way Forwardmentioning

confidence: 99%

Scaffold-free cell-based tissue engineering therapies: advances, shortfalls and forecast

2021

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Cell-based scaffold-free therapies seek to develop in vitro organotypic three-dimensional (3D) tissue-like surrogates, capitalising upon the inherent capacity of cells to create tissues with efficiency and sophistication that is still unparalleled by human-made devices. Although automation systems have been realised and (some) success stories have been witnessed over the years in clinical and commercial arenas, in vitro organogenesis is far from becoming a standard way of care. This limited technology transfer is largely attributed to scalability-associated costs, considering that the development of a borderline 3D implantable device requires very high number of functional cells and prolonged ex vivo culture periods. Herein, we critically discuss advancements and shortfalls of scaffold-free cell-based tissue engineering strategies, along with pioneering concepts that have the potential to transform regenerative and reparative medicine.

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Human skin equivalents cultured under hypoxia display enhanced epidermal morphogenesis and lipid barrier formation

Cited by 36 publications

References 64 publications

Unravelling effects of relative humidity on lipid barrier formation in human skin equivalents

Unravelling effects of relative humidity on lipid barrier formation in human skin equivalents

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Scaffold-free cell-based tissue engineering therapies: advances, shortfalls and forecast

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