Biofabrication of a tri-layered 3D-bioprinted CSC-based malignant melanoma model for personalized cancer treatment

Conventional in vitro cancer models do not accurately reproduce the tumor microenvironment (TME), so three-dimensional (3D)-bioprinting represents an excellent tool to overcome their limitations. Here, two multicellular tri-layered malignant melanoma (MM) models composed by cancer stem cells (CSCs) isolated from a MM established cell line or a primary-patient derived cell line, fibroblasts, mesenchymal stem cells, and endothelial cells, embedded within an agarose-collagen type I hydrogel were bioprinted. Embedded-cells showed high proliferation and metabolic activity, and actively remodeled their TME. MM hydrogels displayed similar rheological properties that skin and were able to support an early onset of vascularization. Besides, MM hydrogels displayed different response to vemurafenib compared with cell cultures, and supported tumorigenesis in murine xenotransplant achieving more mimetic in vivo models. For the first time a tri-layered 3D-bioprinted CSC-based human MM model is developed recreating TME in vitro and in vivo and response to treatment, being useful for precision treatment regimens against MM.

Automated summary

Conventional in vitro cancer models are not able to accurately mimic the tumor microenvironment (TME). In this study, two multicellular tri-layered malignant melanoma (MM) models were bioprinted using cancer stem cells (CSCs), fibroblasts, mesenchymal stem cells, and endothelial cells. The embedded cells exhibited high proliferation, metabolic activity, and TME remodeling. The MM hydrogels displayed similar properties to skin and supported early vascularization. Furthermore, the MM hydrogels showed different response to treatment compared to cell cultures and were able to support tumorigenesis in murine xenotransplant, making them more mimetic of in vivo models.