author_facet Smits, Jos P. H.
Niehues, Hanna
Rikken, Gijs
van Vlijmen-Willems, Ivonne M. J. J.
van de Zande, Guillaume W. H. J. F.
Zeeuwen, Patrick L. J. M.
Schalkwijk, Joost
van den Bogaard, Ellen H.
Smits, Jos P. H.
Niehues, Hanna
Rikken, Gijs
van Vlijmen-Willems, Ivonne M. J. J.
van de Zande, Guillaume W. H. J. F.
Zeeuwen, Patrick L. J. M.
Schalkwijk, Joost
van den Bogaard, Ellen H.
author Smits, Jos P. H.
Niehues, Hanna
Rikken, Gijs
van Vlijmen-Willems, Ivonne M. J. J.
van de Zande, Guillaume W. H. J. F.
Zeeuwen, Patrick L. J. M.
Schalkwijk, Joost
van den Bogaard, Ellen H.
spellingShingle Smits, Jos P. H.
Niehues, Hanna
Rikken, Gijs
van Vlijmen-Willems, Ivonne M. J. J.
van de Zande, Guillaume W. H. J. F.
Zeeuwen, Patrick L. J. M.
Schalkwijk, Joost
van den Bogaard, Ellen H.
Scientific Reports
Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
Multidisciplinary
author_sort smits, jos p. h.
spelling Smits, Jos P. H. Niehues, Hanna Rikken, Gijs van Vlijmen-Willems, Ivonne M. J. J. van de Zande, Guillaume W. H. J. F. Zeeuwen, Patrick L. J. M. Schalkwijk, Joost van den Bogaard, Ellen H. 2045-2322 Springer Science and Business Media LLC Multidisciplinary http://dx.doi.org/10.1038/s41598-017-12041-y <jats:title>Abstract</jats:title><jats:p>The strong societal urge to reduce the use of experimental animals, and the biological differences between rodent and human skin, have led to the development of alternative models for healthy and diseased human skin. However, the limited availability of primary keratinocytes to generate such models hampers large-scale implementation of skin models in biomedical, toxicological, and pharmaceutical research. Immortalized cell lines may overcome these issues, however, few immortalized human keratinocyte cell lines are available and most do not form a fully stratified epithelium. In this study we compared two immortalized keratinocyte cell lines (N/TERT1, N/TERT2G) to human primary keratinocytes based on epidermal differentiation, response to inflammatory mediators, and the development of normal and inflammatory human epidermal equivalents (HEEs). <jats:italic>Stratum corneum</jats:italic> permeability, epidermal morphology, and expression of epidermal differentiation and host defence genes and proteins in N/TERT-HEE cultures was similar to that of primary human keratinocytes. We successfully generated N/TERT-HEEs with psoriasis or atopic dermatitis features and validated these models for drug-screening purposes. We conclude that the N/TERT keratinocyte cell lines are useful substitutes for primary human keratinocytes thereby providing a biologically relevant, unlimited cell source for <jats:italic>in vitro</jats:italic> studies on epidermal biology, inflammatory skin disease pathogenesis and therapeutics.</jats:p> Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models Scientific Reports
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title Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_unstemmed Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_full Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_fullStr Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_full_unstemmed Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_short Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_sort immortalized n/tert keratinocytes as an alternative cell source in 3d human epidermal models
topic Multidisciplinary
url http://dx.doi.org/10.1038/s41598-017-12041-y
publishDate 2017
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description <jats:title>Abstract</jats:title><jats:p>The strong societal urge to reduce the use of experimental animals, and the biological differences between rodent and human skin, have led to the development of alternative models for healthy and diseased human skin. However, the limited availability of primary keratinocytes to generate such models hampers large-scale implementation of skin models in biomedical, toxicological, and pharmaceutical research. Immortalized cell lines may overcome these issues, however, few immortalized human keratinocyte cell lines are available and most do not form a fully stratified epithelium. In this study we compared two immortalized keratinocyte cell lines (N/TERT1, N/TERT2G) to human primary keratinocytes based on epidermal differentiation, response to inflammatory mediators, and the development of normal and inflammatory human epidermal equivalents (HEEs). <jats:italic>Stratum corneum</jats:italic> permeability, epidermal morphology, and expression of epidermal differentiation and host defence genes and proteins in N/TERT-HEE cultures was similar to that of primary human keratinocytes. We successfully generated N/TERT-HEEs with psoriasis or atopic dermatitis features and validated these models for drug-screening purposes. We conclude that the N/TERT keratinocyte cell lines are useful substitutes for primary human keratinocytes thereby providing a biologically relevant, unlimited cell source for <jats:italic>in vitro</jats:italic> studies on epidermal biology, inflammatory skin disease pathogenesis and therapeutics.</jats:p>
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author Smits, Jos P. H., Niehues, Hanna, Rikken, Gijs, van Vlijmen-Willems, Ivonne M. J. J., van de Zande, Guillaume W. H. J. F., Zeeuwen, Patrick L. J. M., Schalkwijk, Joost, van den Bogaard, Ellen H.
author_facet Smits, Jos P. H., Niehues, Hanna, Rikken, Gijs, van Vlijmen-Willems, Ivonne M. J. J., van de Zande, Guillaume W. H. J. F., Zeeuwen, Patrick L. J. M., Schalkwijk, Joost, van den Bogaard, Ellen H., Smits, Jos P. H., Niehues, Hanna, Rikken, Gijs, van Vlijmen-Willems, Ivonne M. J. J., van de Zande, Guillaume W. H. J. F., Zeeuwen, Patrick L. J. M., Schalkwijk, Joost, van den Bogaard, Ellen H.
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description <jats:title>Abstract</jats:title><jats:p>The strong societal urge to reduce the use of experimental animals, and the biological differences between rodent and human skin, have led to the development of alternative models for healthy and diseased human skin. However, the limited availability of primary keratinocytes to generate such models hampers large-scale implementation of skin models in biomedical, toxicological, and pharmaceutical research. Immortalized cell lines may overcome these issues, however, few immortalized human keratinocyte cell lines are available and most do not form a fully stratified epithelium. In this study we compared two immortalized keratinocyte cell lines (N/TERT1, N/TERT2G) to human primary keratinocytes based on epidermal differentiation, response to inflammatory mediators, and the development of normal and inflammatory human epidermal equivalents (HEEs). <jats:italic>Stratum corneum</jats:italic> permeability, epidermal morphology, and expression of epidermal differentiation and host defence genes and proteins in N/TERT-HEE cultures was similar to that of primary human keratinocytes. We successfully generated N/TERT-HEEs with psoriasis or atopic dermatitis features and validated these models for drug-screening purposes. We conclude that the N/TERT keratinocyte cell lines are useful substitutes for primary human keratinocytes thereby providing a biologically relevant, unlimited cell source for <jats:italic>in vitro</jats:italic> studies on epidermal biology, inflammatory skin disease pathogenesis and therapeutics.</jats:p>
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spelling Smits, Jos P. H. Niehues, Hanna Rikken, Gijs van Vlijmen-Willems, Ivonne M. J. J. van de Zande, Guillaume W. H. J. F. Zeeuwen, Patrick L. J. M. Schalkwijk, Joost van den Bogaard, Ellen H. 2045-2322 Springer Science and Business Media LLC Multidisciplinary http://dx.doi.org/10.1038/s41598-017-12041-y <jats:title>Abstract</jats:title><jats:p>The strong societal urge to reduce the use of experimental animals, and the biological differences between rodent and human skin, have led to the development of alternative models for healthy and diseased human skin. However, the limited availability of primary keratinocytes to generate such models hampers large-scale implementation of skin models in biomedical, toxicological, and pharmaceutical research. Immortalized cell lines may overcome these issues, however, few immortalized human keratinocyte cell lines are available and most do not form a fully stratified epithelium. In this study we compared two immortalized keratinocyte cell lines (N/TERT1, N/TERT2G) to human primary keratinocytes based on epidermal differentiation, response to inflammatory mediators, and the development of normal and inflammatory human epidermal equivalents (HEEs). <jats:italic>Stratum corneum</jats:italic> permeability, epidermal morphology, and expression of epidermal differentiation and host defence genes and proteins in N/TERT-HEE cultures was similar to that of primary human keratinocytes. We successfully generated N/TERT-HEEs with psoriasis or atopic dermatitis features and validated these models for drug-screening purposes. We conclude that the N/TERT keratinocyte cell lines are useful substitutes for primary human keratinocytes thereby providing a biologically relevant, unlimited cell source for <jats:italic>in vitro</jats:italic> studies on epidermal biology, inflammatory skin disease pathogenesis and therapeutics.</jats:p> Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models Scientific Reports
spellingShingle Smits, Jos P. H., Niehues, Hanna, Rikken, Gijs, van Vlijmen-Willems, Ivonne M. J. J., van de Zande, Guillaume W. H. J. F., Zeeuwen, Patrick L. J. M., Schalkwijk, Joost, van den Bogaard, Ellen H., Scientific Reports, Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models, Multidisciplinary
title Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_full Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_fullStr Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_full_unstemmed Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_short Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
title_sort immortalized n/tert keratinocytes as an alternative cell source in 3d human epidermal models
title_unstemmed Immortalized N/TERT keratinocytes as an alternative cell source in 3D human epidermal models
topic Multidisciplinary
url http://dx.doi.org/10.1038/s41598-017-12041-y