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Directly reprogrammed renal cells for targeted medicine

Project description

In vitro renal tissue generation for targeted medicine

The global incidence of kidney disease is on the rise, and new methods to create renal tissue in vitro are urgently needed. The EU-funded DiRECT project aims to use direct reprogramming to generate renal cells to better understand kidney disease and develop therapeutic options. In principle, cell reprogramming could be used for establishing the patient-specific kidney cells to evaluate potential therapeutic targets in the laboratory. The objectives include understanding the mechanism of the cell-type conversion process, optimisation of the reprogramming process, and further directing of the reprogramming towards more specialised cell types. Finally, the project will investigate the molecular mechanisms of human genetic kidney conditions to identify therapeutic targets for these diseases.


The global incidence of kidney disease is on the rise, but little progress has been made to develop novel therapies or preventative measures.
New methods to generated renal tissue in vitro hold great promise for regenerative medicine and the prospect of organ replacement. Most of the strategies employed differentiate induced pluripotent stem cells (iPSCs) into kidney organoids, which can be derived from patient tissue.
Direct reprogramming is an alternative approach to convert one cell type into another using cell fate specifying transcription factors. We were the first to develop a method to directly reprogram mouse and human fibroblasts to kidney cells (induced renal tubular epithelial cells - iRECs) without the need for pluripotent cells. Morphological, transcriptomic and functional analyses found that directly reprogrammed iRECs are remarkably similar to native renal tubular cells. Direct reprogramming is fast, technically simple and scalable.
This proposal aims to establish direct reprogramming in nephrology and develop novel in vitro models for kidney diseases that primarily affect the renal tubules. We will unravel the mechanics of how only four transcription factors can change the morphology and function of fibroblasts towards a renal tubule cell identity. These insights will be used to identify alternative routes to directly reprogram tubule cells with increased efficiency and accuracy. We will identify cell type specifying factors for reprogramming of tubular segment specific cell types. Finally, we will use of reprogrammed kidney cells to establish new in vitro models for autosomal dominant polycystic kidney disease and nephronophthisis.
Direct reprogramming holds enormous potential to deliver patient specific disease models for diagnostic and therapeutic applications in the age of personalized and targeted medicine.

Host institution

Net EU contribution
€ 1 499 917,00
8006 Zurich

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Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
Total cost
€ 1 499 917,00

Beneficiaries (1)