In many cases promising results of cell culture experiments lead to a disappointing outcome when transferred to animal experiments or human clinical studies. The reason therefore is obvious. The gap between a two-dimensional cell culture experiment and a complete organism is difficult to bridge, thus results can hardly be related. Aim of this project is the verification of a 3D Organ Lab Model which helps to investigate biochemical processes and their pathologies in complete organs. This project focuses on the establishment of a blood vessel model, a placenta model, and a model of the gut by the use of the 3D Organ Lab Model. Already available three-dimensional systems or organ culture models lack flexibility and do not respond to the needs of specialized cells in a three-dimensional network. This model combines following advantages: 1) Different cell types are composed 2) in a three-dimensional network and could be cultivated 3) in defined regions 4) with diverse physical and chemical conditions, wherein 5) direct cell-to-cell contact can be promoted or avoided.
This model consists of an electrospun hollow fiber of polycaprolactone modified with polylactide (PCL/PLA). The hollow fiber is fixed in a polycarbonate housing to create two discriminative compartments -the inner surface facing the lumen, representing the inner compartment and a second (outer) compartment. Both can be seeded with cells from various tissues. The PCL/PLA mesh allows a cross-talk of cells by the exchange of paracrine factors or could offer a direct cell-to-cell contact. The cells in the inner and outer compartment are applied to conditions appropriate to their requirements, e.g. flow, nutrition supplies, or variations in the oxygen concentration.
The blood vessel model will consist of endothelial cells in the inner compartment and will be perfused with monocytes to simulate the human blood flow. The influence of mesenchymal stem cells in the outer compartment on the migration of the activated monocytes will be investigated.
The placenta model will consist of endothelial and trophoblast cells in different compartments with different oxygen supply. The influence of IL-6 in trophoblast invasion will be investigated.
The model of the gut will consist of colon cells co-cultivated with mucus producing HT29-MTX. The influence of alcohol, faecal slurries, or silenced CFTR gene on the regulation of tight-junctions will be investigated by the determination of tight-junction proteins and bacterial translocation studies.