Development of novel models of kidney damage using induced human pluripotent stem cells

Developing differentiation methods to generate kidney organoid models offer a new perspective to investigate kidney development and disease. A method ford ifferentiating P019 L47, an iPSc cell line derived from mononuclear blood cells to kidney organoids, was generated based on previously published kidney organoid protocols. The kidney organoids were characterised via qPCR, Westernblot, H&E staining and immunofluorescence to confirm the presence of posterior and anterior intermediate mesoderm cell populations and intermediated mesoderm derived architecture.

Preliminary work to generate a GREM1 reduced kidney organoid model began by investigated the use of small molecule inhibitors to prevent GREM1 antagonism. Of the compounds tested by luciferase assay small molecule inhibitor 04_A was the only compound to be able to significantly inhibit GREM1 to ‘rescue’ BMP2 signalling. The next step in creating a GREM1 kidney organoid model would involve developing a robust method to measure GREM1 activity within the kidney organoids followed by treating 04_Ato differentiating kidney organoids to investigate GREM1 role during nephrogenesis.</p><p></p>