title: Tissue engineering of a human 3D in vitro tumor test system.
abstract: 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 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.
authors: Department of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg.
authors: Corinna
authors: C
authors: Moll
authors: Jenny
authors: J
authors: Reboredo
authors: Thomas
authors: T
authors: Schwarz
authors: Antje
authors: A
authors: Appelt
authors: Sebastian
authors: S
authors: Schürlein
authors: Heike
authors: H
authors: Walles
authors: Sarah
authors: S
authors: Nietzer
mesh_terms: D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D045744:Cell Line, Tumor; D006801:Humans; D018317:Nerve Sheath Neoplasms / Q000473:pathology*; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*
references: Cell. 2011 Mar 4;144(5):646-74
references: 21376230
references: Tissue Eng. 2007 Nov;13(11):2699-707
references: 17867928
references: Ann Biomed Eng. 2003 Oct;31(9):1017-30
references: 14582605
references: J Cell Biol. 1997 Apr 7;137(1):231-45
references: 9105051
references: Curr Opin Drug Discov Devel. 2008 Jan;11(1):111-27
references: 18175274
references: J Biotechnol. 2010 Jul 1;148(1):56-63
references: 20399817
references: Adv Drug Deliv Rev. 2011 Apr 30;63(4-5):195-6
references: 21600252
references: Trends Biotechnol. 2004 Feb;22(2):80-6
references: 14757042
references: J Urol. 2005 Jan;173(1):276-80
references: 15592096
references: Biomaterials. 2011 Oct;32(30):7469-78
references: 21764120
references: J Cell Mol Med. 2009 Aug;13(8A):1417-27
references: 19627398
references: Biomaterials. 2005 Nov;26(33):6610-7
references: 15979139
references: Neoplasia. 2007 Aug;9(8):671-7
references: 17786186
references: Cell. 2007 Aug 24;130(4):601-10
references: 17719539