Biofabrication of a tri-layered 3D-bioprinted CSC-based malignant melanoma model for personalized cancer treatment
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Materia
3D bioprinting Tumor Microenvironment Malignant melanoma Tumor model Melanoma 3D model
Date
2023-05-15Referencia bibliográfica
Julia López de Andrés et al 2023 Biofabrication 15 035016 [DOI 10.1088/1758-5090/ac8dc6]
Sponsorship
Consejería de Salud y Familias de la Junta de Andalucía (Project No. PIN-0224-2019); Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía (FEDER Funds, Projects PY18-FR-2470, B-CTS-230-UGR18, A-CTS-180-UGR20, PYC20 RE 015 UGR and P18-FR-2465),; Ministry de Economía y Competitividad, Instituto de Salud Carlos III (FEDER funds, Projects Nos. DTS19/00145 and DTS21/00098); Chair ‘Doctors Galera-Requena in cancer stem cell research’ (CMCCTS963); Universidad de Granada/CBUA.; Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020— FEDER funds—Ref: DOC_01574).Abstract
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.