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Tissue Engineering of a Human 3D in vitro Tumor Test System

Please always quote using this URN: urn:nbn:de:bvb:20-opus-132277
  • Cancer is one of the leading causes of death worldwide. Current therapeutic strategies are predominantly developed in 2D culture systems, which inadequately reflect physiological conditions in vivo. Biological 3D matrices provide cells an environment in which cells can self-organize, allowing the study of tissue organization and cell differentiation. Such scaffolds can be seeded with a mixture of different cell types to study direct 3D cell-cell-interactions. To mimic the 3D complexity of cancer tumors, our group has developed a 3D in vitroCancer is one of the leading causes of death worldwide. Current therapeutic strategies are predominantly developed in 2D culture systems, which inadequately reflect physiological conditions in vivo. Biological 3D matrices provide cells an environment in which cells can self-organize, allowing the study of tissue organization and cell differentiation. Such scaffolds can be seeded with a mixture of different cell types to study direct 3D cell-cell-interactions. To mimic the 3D complexity of cancer tumors, our group has developed a 3D in vitro tumor test system. Our 3D tissue test system models the in vivo situation of malignant peripheral nerve sheath tumors (MPNSTs), which we established with our decellularized porcine jejunal segment derived biological vascularized scaffold (BioVaSc). In our model, we reseeded a modified BioVaSc matrix with primary fibroblasts, microvascular endothelial cells (mvECs) and the S462 tumor cell line For static culture, the vascular structure of the BioVaSc is removed and the remaining scaffold is cut open on one side (Small Intestinal Submucosa SIS-Muc). The resulting matrix is then fixed between two metal rings (cell crowns). Another option is to culture the cell-seeded SIS-Muc in a flow bioreactor system that exposes the cells to shear stress. Here, the bioreactor is connected to a peristaltic pump in a self-constructed incubator. A computer regulates the arterial oxygen and nutrient supply via parameters such as blood pressure, temperature, and flow rate. This setup allows for a dynamic culture with either pressure-regulated pulsatile or constant flow. In this study, we could successfully establish both a static and dynamic 3D culture system for MPNSTs. The ability to model cancer tumors in a more natural 3D environment will enable the discovery, testing, and validation of future pharmaceuticals in a human-like model.show moreshow less

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Metadaten
Author: Corinna Moll, Jenny Reboredo, Thomas Schwarz, Antje Appelt, Sebastian Schürlein, Heike Walles, Sarah Nietzer
URN:urn:nbn:de:bvb:20-opus-132277
Document Type:Journal article
Faculties:Medizinische Fakultät / Lehrstuhl für Tissue Engineering und Regenerative Medizin
Language:English
Parent Title (English):Journal of Visualized Experiments
Year of Completion:2013
Volume:78
Issue:e50460
Source:Journal of Visualized Experiments (78), e50460, doi:10.3791/50460 (2013)
URL:http://www.jove.com/video/50460
DOI:https://doi.org/10.3791/50460
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:3D in vitro models; BioVaSc; anatomy; bioengineering; biomedical engineering; bioreactor; biotechnology; cell culture; cell engineering; cellular biology; cellular microenvironment; culture techniques; cultured; decellularization; dynamic culture conditions; equipment and supplies; molecular biology; physiology; primary cell isolation; tissue engineering; tumor cells; tumor test system
Release Date:2016/06/11
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitung