A tissue engineering approach to reduce animal use in renal development and renal organ replacement technology

Kidney disease is a major cause of suffering worldwide and treating it is a great drain on the resources of healthcare systems such as the NHS. This is because kidneys are not capable of repairing many types of defect. There is therefore a great deal of research, in the UK, USA and Europe, aimed at finding ways to repair damaged kidneys or to grow new ones. It is clear, though, that we have to understand more about how kidneys form in the first place, when a human is still in the womb, before we know enough to build or rebuild them in the lab or the clinic. Research into how kidneys grow currently uses animals, either in fully animal-based experiments or in test-tube experiments that use the kidneys of freshly-killed animal embryos. The test-tube technique is useful, but still quite limited. This project aims to produce cells that can be grown in the lab indefinitely, and combined together to produce emrbyo kidneys in the test tube without any animals being needed. It will not only greatly reduce the use of animals in this type of research, which is the main point - it will also provide a system in which doing experiments is much quicker, easier and cheaper,. It will therefore speed along the pace of discovery in this area of research so important to human medicine.

This project has two aims; (1) to Replace animals in an important field of research and (2) to develop a superior culture system for renal tissue engineering. Research into renal regeneration and renal replacement therapy is growing rapidly, driven by urgent clinical need. It is clear, however, that advance will depend on a better understanding of signalling and lineage in normal renal development. These are being investigated in a variety of ways, all of which use animals, either in vivo or by organ culture of kidneys isolated from embryos. The organ culture system has proved particularly useful, but is still limited in its ability to allow manipulation of gene expression. This project aims to produce cell lines that can give rise to specific components of the kidney in an organotypic setting, and can reconstitute a whole emrbyonic kidney in combination. Based on our existing systems, we will produce these cell lines both by conditional immortalization of cells from embryonic kidneys and by sorting and culture of ES cell derivatives. We will assess the fates available to each line in an organotypic context and will assess their ability to produce renal structures, up to a whole kidney, in movel tissue engineering culture systems based on our current state-of-the-art. This project brings togethetr the expertise of three laboratories to achieve a significant advance in both the 3Rs and in renal regeneration and replacement by tissue engineering.