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Introduction to Kidney Development
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Hypotheses
- It is possible to induce embryonic and / or adult stem cells to adopt a renal progenitor fate.
- Isolation of these renal progenitor cells can be achieved via sorting for specific cell surface markers.
- Renal stem cells administered to patients with or at risk of end stage renal disease (ESRD) can be recruited to, and functionally integrated into, the damaged kidney.
- Glomerular and tubulo-interstitial damage in the ESRD kidney can be repaired by the administration of embryonic stem cell-derived or patient-derived renal progenitor cells.
To reach these long term clinical objectives, we propose the following basic research objectives:
- Use expression profiling to further dissect the processes of commitment to a metanephric fate during normal development
- Identify novel renal progenitor cell markers and growth factors to assist in the identification, isolation and / or reactivation of renal stem cells.
- Examine the potential for embryonic stem cells to be differentiated into the lineages necessary for renal regeneration or endogenous repair.
The research projects within this application approach the problem from both the bottom up and top down. From the top down, we aim to characterise the expression profile of different renal subcompartments so as to identify the secreted proteins involved in renal differentiation and to isolate the specific cell surface markers identifying 'renal stem cells'. Expression profiles will be subjected to targeted bioinformatic screening so as to rapidly identify secreted and transmembrane proteins. From the bottom up , we aim to induce embryonic stem cells to adopt a renal fate using co-culture with cell lines, metanephroi and novel growth factors. The power of this approach lies in the combination of molecular genetics, bioinformatics and stem cell biology.
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