Tissue-engineered 3D melanoma model with blood and lymphatic capillaries for drug development
抄録
<jats:title>Abstract</jats:title><jats:p>While being the rarest skin cancer, melanoma is also the deadliest. To further drug discovery and improve clinical translation, new human cell-based <jats:italic>in vitro</jats:italic> models are needed. Our work strives to mimic the melanoma microenvironment <jats:italic>in vitro</jats:italic> as an alternative to animal testing. We used the self-assembly method to produce a 3D human melanoma model exempt of exogenous biomaterial. This model is based on primary human skin cells and melanoma cell lines while including a key feature for tumor progression: blood and lymphatic capillaries. Major components of the tumor microenvironment such as capillaries, human extracellular matrix, a stratified epidermis (involucrin, filaggrin) and basement membrane (laminin 332) are recapitulated <jats:italic>in vitro</jats:italic>. We demonstrate the persistence of CD31<jats:sup>+</jats:sup> blood and podoplanin<jats:sup>+</jats:sup>/LYVE-1<jats:sup>+</jats:sup> lymphatic capillaries in the engineered tissue. Chronic treatment with vemurafenib was applied to the model and elicited a dose-dependent response on proliferation and apoptosis, making it a promising tool to test new compounds in a human-like environment.</jats:p>
収録刊行物
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- Scientific Reports
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Scientific Reports 8 (1), 2018-09-04
Springer Science and Business Media LLC