This project will focus on the production of an in vitro human disease tissue platform technology to enable and accelerate the development of regenerative medicine therapies for a diverse range of diseases. The concept will be realised by the in vitro generation of 3D human tissues cultured from human induced Pluripotent Stem (iPS) cells. Initially a library of adult cells will be generated from patients with a range of genetic diseases. These cells will subsequently be used to generate iPS cell cultures in optimised conditions, with the resultant cells being differentiated into key cell types. These differentiated cells will then be integrated onto 3D tissue bioreactors operating in an optimised variable perfusion environment producing the 3D human tissue disease cultures. The bioreactors will be constructed using a range of innovative microfluidic techniques to produce systems compatible with analysis systems commonly used in laboratories worldwide. The development of a platform technology producing 3D human tissue disease cultures will enable the generation of fully differentiated cell types and thus allow diseases to be effectively modelled at a population relevant scale in 3D human tissues in vitro. The resultant major benefit of the system is that it will allow regenerative therapies to be developed and tested on batteries of human tissues in the laboratory in a rapid, cost effective manner relevant to the in vivo state. To develop and validate the platform technology within the lifetime of the project liver hepatocyte cells and tissues will be generated due to their scientific and commercial significance from a population relevant range of patients with inherited metabolic disorders (IMDs). Therefore this project will significantly advance the state of the art and constitute a significant step forward for the regenerative medicine industry producing a key platform resource.
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