Tissue Engineering of a Human 3D <em>in vitro</em> 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.

Fabrication of Biodegradable Synthetic Vascular Networks and Their Use as a Model of Angiogenesis

“…In an attempt to understand the fundamental principles behind the induction of angiogenesis, development of 3D models investigating the interactions between different cell types has progressed [Mon- , 1993;Donovan et al, 2001;Santos et al, 2008]. Other studies have looked at the influence of fluid flow on EC survival and sprouting [Moll et al, 2013;VukadinovicNikolic et al, 2014]. However, we are unaware of any models that have the ability to combine different cell combinations and fluid flow to investigate the induction of earlystage blood vessel formation for TE applications.…”

A multilayered electrospun graft as vascular access for hemodialysis

“…For static culture, vascular grafts were placed in a cell crown culture system consisting of two metal rings according to Moll et al [16] Therefore, sterilized vascular scaffolds were opened on one side, cut in pieces of approximately 1 cm 2 , and placed onto the smaller inner ring of a metal crown. Following, scaffolds were clamped by placing the bigger outer ring above the inner ring.…”

The role of receptor tyrosine kinase EphB4 in the tumorigenesis of endometrial cancer

“…Discrepancy between our results and the results presented by Eritja and colleagues (Eritja et al, 2010) could be due to the origin and type of endometrial epithelial cells used in the modelling, in which they used normal mouse endometrial epithelial cells whereas we used human endometrial cancer cells. In addition, endometrial epithelial cells modelled in 3D rBM and 3D poly-HEMA systems showed reduced proliferation as compared to cells grown in 2D, which is similar to findings from other groups (Fallica et al, 2012, Moll et al, 2013. Furthermore, in either of these two types of 3D culture systems distinctive phenotypes of MCSs were presented by different endometrial epithelial cell lines, which recapitulate to some extent certain biological features of neoplastic transformation and progression of endometrial epithelial cells.…”