Three-dimensional bioprinting for the construction of an in vitro gastrointestinal stromal tumor model

Traditional two-dimensional (2D) cell culture systems are inadequate for maintaining numerous intrinsic cellular characteristics inherent to the native three-dimensional (3D) in vivo environment, which can result in misleading experimental outcomes. Hence, there is an urgent demand for innovative 3D tumor models that can be reliably employed in preclinical investigations. As an additive manufacturing technique, 3D bioprinting enables the fabrication of biomimetic 3D structures using a variety of materials, cells, and other small-molecule substances. This capability enables the fabrication of complex biomimetic tissue-like architectures. In this study, we developed an advanced 3D tumor model using 3D bioprinting technology to investigate the phenotypic and molecular expression profiles of gastrointestinal stromal tumor (GIST) cells within this engineered microenvironment. Our findings show that cells within the bioprinted constructs maintained high viability over an extended period following printing. In comparison to conventional 2D monolayer cultures, GIST cells cultured in the 3D bioprinted system exhibited significantly enhanced metabolic activity and improved long-term cell survival. Furthermore, the 3D bioprinted environment promoted cell proliferation and upregulated the expression of key tumor-associated genes. In vivo transplantation experiments revealed markedly higher tumorigenic potential in the 3D bioprinted group relative to the 2D control group. Overall, our 3D bioprinting model effectively recapitulates critical aspects of clinical tumor behavior and disease-relevant phenotypes of GIST. This platform holds strong potential as a highly predictive preclinical tool for drug screening and translational research of GIST, offering a promising alternative to animal testing.