3D human tissue models in regenerative medicine
The mission of the EU-funded TISSUEGEN (The production of a 3D human tissue disease platform to enable regenerative medicine therapy development) project was the development of an in vitro human disease tissue platform technology for regenerative therapy. The concept is based on the in vitro generation of 3D human tissues cultured from human IPSCs. Liver hepatocytes and tissues have been designated for the validation phase due to their scientific and commercial significance. Researchers established a bank of human IPSCs and embryonic stem cells from healthy and diseased donors with inherited metabolic disorders. They optimised protocols for the differentiation of these cells into hepatocytes. Obtained human hepatocytes were further investigated in the 3D liver tissue platform. The function of stem cell-derived hepatocytes was significantly enhanced when tested in the format of 3D culture in comparison with the same lot of cells in 2D culture. The 3D disease models were subsequently developed using IPSC hepatocytes and cholangiocytes to model glycogen storage disease, cystic fibrosis and others. The cystic fibrosis model recapitulated the key aspects of the disease and provided a unique platform to model the biliary disease induced by this condition. In conclusion, the project has produced commercially available stem cell derived hepatocytes and a high throughput organ-on-a chip (LiverChip®) device. The 3D disease models are important as they could be used to identify and modulate new targets in the disease pathways. The healthy cell models, however, can be further developed into a useful tool for toxicological screening.
Keywords
3D human tissue model, regenerative medicine, stem cell, TISSUEGEN, hepatocytes, LiverChip®
