A preclinical model of cutaneous melanoma based on reconstructed human epidermis.

Autor: Leikeim A; Department Tissue Engineering & Regenerative Medicine (TERM), University Hospital Würzburg, Röntgenring 11, 97070, Würzburg, Germany., Wußmann M; Translational Center for Regenerative Therapies TLZ-RT, Fraunhofer-Institute for Silicate Research ISC, Würzburg, Germany., Schmidt FF; Translational Center for Regenerative Therapies TLZ-RT, Fraunhofer-Institute for Silicate Research ISC, Würzburg, Germany., Neto NGB; Department of Mechanical, Manufacturing and Biomedical Engineering, Trinity College Dublin, Dublin, Ireland.; Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland., Benz F; Department Tissue Engineering & Regenerative Medicine (TERM), University Hospital Würzburg, Röntgenring 11, 97070, Würzburg, Germany.; Translational Center for Regenerative Therapies TLZ-RT, Fraunhofer-Institute for Silicate Research ISC, Würzburg, Germany., Tiltmann K; Translational Center for Regenerative Therapies TLZ-RT, Fraunhofer-Institute for Silicate Research ISC, Würzburg, Germany., Junger C; Department Tissue Engineering & Regenerative Medicine (TERM), University Hospital Würzburg, Röntgenring 11, 97070, Würzburg, Germany.; Translational Center for Regenerative Therapies TLZ-RT, Fraunhofer-Institute for Silicate Research ISC, Würzburg, Germany., Monaghan MG; Department of Mechanical, Manufacturing and Biomedical Engineering, Trinity College Dublin, Dublin, Ireland.; Trinity Centre for Biomedical Engineering, Trinity College Dublin, Dublin, Ireland.; Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin, Ireland.; CÚRAM, Centre for Research in Medical Devices, National University of Ireland, Newcastle Road, Galway, H91 W2TY, Ireland., Schilling B; Department of Dermatology, University Hospital Würzburg, Würzburg, Germany., Groeber-Becker FK; Department Tissue Engineering & Regenerative Medicine (TERM), University Hospital Würzburg, Röntgenring 11, 97070, Würzburg, Germany. florian.groeber-becker@isc.fraunhofer.de.; Translational Center for Regenerative Therapies TLZ-RT, Fraunhofer-Institute for Silicate Research ISC, Würzburg, Germany. florian.groeber-becker@isc.fraunhofer.de.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Sep 29; Vol. 12 (1), pp. 16269. Date of Electronic Publication: 2022 Sep 29.
DOI: 10.1038/s41598-022-19307-0
Abstrakt: Malignant melanoma is among the tumor entities with the highest increase of incidence worldwide. To elucidate melanoma progression and develop new effective therapies, rodent models are commonly used. While these do not adequately reflect human physiology, two-dimensional cell cultures lack crucial elements of the tumor microenvironment. To address this shortcoming, we have developed a melanoma skin equivalent based on an open-source epidermal model. Melanoma cell lines with different driver mutations were incorporated into these models forming distinguishable tumor aggregates within a stratified epidermis. Although barrier properties of the skin equivalents were not affected by incorporation of melanoma cells, their presence resulted in a higher metabolic activity indicated by an increased glucose consumption. Furthermore, we re-isolated single cells from the models to characterize the proliferation state within the respective model. The applicability of our model for tumor therapeutics was demonstrated by treatment with a commonly used v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor vemurafenib. This selective BRAF inhibitor successfully reduced tumor growth in the models harboring BRAF-mutated melanoma cells. Hence, our model is a promising tool to investigate melanoma development and as a preclinical model for drug discovery.
(© 2022. The Author(s).)
Databáze: MEDLINE
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