期刊
BIOFABRICATION
卷 14, 期 3, 页码 -出版社
IOP Publishing Ltd
DOI: 10.1088/1758-5090/ac5fb7
关键词
neuroblastoma; laser manufacturing; fluidic device; vascularization; mesenchymal stem cells; angiogenesis; induced pluripotent stem cell differentiation
资金
- Austrian Science Fund [I3089-B28, FG15]
- Austrian Research Promotion Agency [880666]
- Federal Ministry Republic of Austria for Education, Science and Research
- Kinderkrebshilfe Tirol und Vorarlberg
- Tirol-Kliniken GmbH
- Medical University Innsbruck Project [PTF 2020-1-4]
- Austrian Science Fund (FWF) [FG15] Funding Source: Austrian Science Fund (FWF)
This paper presents a novel 3D printed neuroblastoma-tumor-environment model and a biofabrication platform suitable for studying tumor angiogenesis and metastasis.
Neuroblastoma is an extracranial solid tumor which develops in early childhood and still has a poor prognosis. One strategy to increase cure rates is the identification of patient-specific drug responses in tissue models that mimic the interaction between patient cancer cells and tumor environment. We therefore developed a perfused and micro-vascularized tumor-environment model that is directly bioprinted into custom-manufactured fluidic chips. A gelatin-methacrylate/fibrin-based matrix containing multiple cell types mimics the tumor-microenvironment that promotes spontaneous micro-vessel formation by embedded endothelial cells. We demonstrate that both, adipocyte- and iPSC-derived mesenchymal stem cells can guide this process. Bioprinted channels are coated with endothelial cells post printing to form a dense vessel-tissue barrier. The tissue model thereby mimics structure and function of human soft tissue with endothelial cell-coated larger vessels for perfusion and micro-vessel networks within the hydrogel-matrix. Patient-derived neuroblastoma spheroids are added to the matrix during the printing process and grown for more than two weeks. We demonstrate that micro-vessels are attracted by and grow into tumor spheroids and that neuroblastoma cells invade the tumor-environment as soon as the spheroids disrupt. In summary, we describe the first bioprinted, micro-vascularized neuroblastoma-tumor-environment model directly printed into fluidic chips and a novel medium-throughput biofabrication platform suitable for studying tumor angiogenesis and metastasis in precision medicine approaches in future.
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