Tissue-engineered 3D melanoma model with blood and lymphatic capillaries for drug development.
Jennifer BourlandJulie FradetteFrancois A AugerPublished in: Scientific reports (2018)
While being the rarest skin cancer, melanoma is also the deadliest. To further drug discovery and improve clinical translation, new human cell-based in vitro models are needed. Our work strives to mimic the melanoma microenvironment in vitro 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 in vitro. We demonstrate the persistence of CD31+ blood and podoplanin+/LYVE-1+ 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.
Keyphrases
- skin cancer
- endothelial cells
- lymph node
- extracellular matrix
- induced pluripotent stem cells
- drug discovery
- stem cells
- pluripotent stem cells
- cell cycle arrest
- induced apoptosis
- poor prognosis
- machine learning
- signaling pathway
- cell proliferation
- endoplasmic reticulum stress
- single cell
- deep learning
- long non coding rna
- atopic dermatitis
- replacement therapy