Design of spherically structured 3D in vitro tumor models -Advances and prospects. (15th July 2018)

• Record Type: Journal Article
• Authors: Ferreira, L.P.; Gaspar, V.M.; Mano, J.F.
• Is Part Of: Acta biomaterialia. Volume 75(2018)
• Page Start: 11
• Page End: 34
• Publication Date: 2018-07-15
• Subjects: 3D-MCTS Three-dimensional Multicellular Tumor Spheroids -- Tumor-ECM Tumor Extracellular Matrix -- 3D Three-Dimensional -- TME Tumor Microenvironment -- MSCs Mesenchymal Stem Cells -- PLL Poly-L-Lysine -- hADSCs Human Adipose-derived Stem Cells -- ALP Alkaline Phosphatase -- MMPs Matrix Metalloproteinases -- EMT Epithelial-to-Mesenchymal-Transition -- GFP Green Fluorescent Protein -- EGF Epidermal Growth Factor -- bFGF Basic Fibroblast Growth Factor -- PDGF Platelet-Derived Growth Factor -- HyA Hyaluronic Acid -- SDF-1α Stromal Cell-Derived Factor Α -- VEGF Vascular Endothelial Growth Factor -- BMP-2 Bone Morphogenetic Protein 2 -- hBM-MSCs Human Bone-Marrow Derived Mesenchymal Stem Cells -- dECMs Decellularized Matrices -- PEG Poly(ethylene glycol) -- PLA Polylactic Acid -- PGA Poly(Glycolic Acid) -- PLGA Poly(Lactic-co-Glycolic Acid) -- PCL Poly-ɛ-Caprolactone -- PVA Polyvinyl Alcohol -- PS Polystyrene -- CAFs Cancer-Associated Fibroblasts -- PCa-CSCs Prostate Cancer Stem-Like Cells -- HUVECs Human Umbilical Vein Endothelial Cells -- PEGDA Poly(ethylene glycol) Diacrylate -- H&E Hematoxylin-Eosin -- RFP Red Fluorescent Protein; 3D In vitro models -- Drug screening -- Microparticles -- Microcapsules -- Tumor spheroids; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2018.05.034
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Abstract: Three-dimensional multicellular tumor models are receiving an ever-growing focus as preclinical drug-screening platforms due to their potential to recapitulate major physiological features of human tumors in vitro . In line with this momentum, the technologies for assembly of 3D microtumors are rapidly evolving towards a comprehensive inclusion of tumor microenvironment elements. Customized spherically structured platforms, including microparticles and microcapsules, provide a robust and scalable technology to imprint unique biomolecular tumor microenvironment hallmarks into 3D in vitro models. Herein, a comprehensive overview of novel advances on the integration of tumor-ECM components and biomechanical cues into 3D in vitro models assembled in spherical shaped platforms is provided. Future improvements regarding spatiotemporal/mechanical adaptability, and degradability, during microtumors in vitro 3D culture are also critically discussed considering the realistic potential of these platforms to mimic the dynamic tumor microenvironment. From a global perspective, the production of 3D multicellular spheroids with tumor ECM components included in spherical models will unlock their potential to be used in high-throughput screening of therapeutic compounds. It is envisioned, in a near future, that a combination of spherically structured 3D microtumor models with other advanced microfluidic technologies will properly recapitulate the flow dynamics of human tumors in vitro . Statement of Significance: The ability to correctly mimic the complexity of the tumor microenvironment in vitro is a key aspect for the development of evermore realistic in vitro models for drug-screening and fundamental cancer biology studies. In this regard, conventional spheroid-based 3D tumor models, combined with spherically structured biomaterials, opens the opportunity to precisely recapitulate complex cell-extracellular matrix interactions and tumor compartmentalization. This review provides an in-depth focus on current developments regarding spherically structured scaffolds engineered into in vitro 3D tumor models, and discusses future advances toward all-encompassing platforms that may provide an improved in vitro/in vivo correlation in a foreseeable future.