Biofabrication of a Tri-layered 3D-Bioprinted CSC-based Malignant Melanoma Model for Personalized Cancer Treatment.
Julia LopezMarta Ruiz-ToranzoCristina AntichCarlos Chocarro-WronaElena López-RuizGema JiménezJuan Antonio Marchal CorralesPublished in: Biofabrication (2022)
Conventional in vitro cancer models do not accurately reproduce the tumor microenvironment, so 3D-bioprinting represents an excellent tool to overcome their limitations. Here, two multicellular tri-layered malignant melanoma (MM) models composed by cancer stem cells 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.
Keyphrases
- early onset
- endothelial cells
- wound healing
- mesenchymal stem cells
- drug delivery
- tissue engineering
- cancer stem cells
- late onset
- hyaluronic acid
- extracellular matrix
- induced apoptosis
- single cell
- highly efficient
- papillary thyroid
- stem cells
- squamous cell carcinoma
- cell proliferation
- combination therapy
- squamous cell
- young adults
- oxidative stress
- bone marrow
- high glucose
- replacement therapy