Regenerative Medicine Utrecht


21 November 2017

Frans Schutgens

Thesis: Adult Stem Cell-Derived Kidney Organoids to Model Tissue Physiology and Disease

PhD supervisors: Prof. Dr. H.C. Clevers and Prof. Dr. M.C. Verhaar

Defense date: 21 November 2017

Kidney disease is a worldwide public health problem for which no curative treatment exists. A better understanding of kidney function, regeneration and disease is essential to identify new therapeutic targets and reliably test efficacy and toxicity of drugs. To achieve these goals, adequate human in vitro models are indispensable, since mouse models may not fully capture human disease.
An in vitro model system that has been developed over the last decade, is adult stem cell (ASC)-derived organoid culture. The field has developed at a tremendous pace and yielded exciting results for other organs than the kidney. These include personalized medicine for cystic fibrosis (CF) and modeling the development of colon cancer in vitro.  However, such a culture system did not exist for the kidney.
In Frans’ thesis, an ASC-derived kidney organoid culture system was developed and investigated. Two aspects of this system are particularly relevant. First, it allows the expansion of healthy kidney tubular epithelial cells without immortalization or reprogramming. This provides a platform for the study of kidney function that potentially better resembles the in vivo situation than cell lines. Second, it allows the culture of primary diseased cells directly from patients, enabling the heterogeneous culture of tumor cells, disease modeling and personalized medicine. These two features have proved difficult or even impossible with existing in vitro models (cell lines and PSC-derived organoids) making ASC-derived organoids a useful and complementary tool for in vitro kidney research.

PhD Supervisors: Marianne Verhaar & Hans Clevers