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Abstract: FR-OR053

Modelling Immune Mediated Renal Injury through the Use of Induced Pluripotent Stem Cell Derived Organoids

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic


  • Dodd, Thomas K., University College Dublin, Dublin, Ireland
  • Davis, Jessica L., University College Dublin, Dublin, Ireland
  • Kennedy, Ciarán, University College Dublin, Dublin, Ireland
  • Clerkin, Shane, UCD, Dublin, Ireland
  • De gaetano, Monica, University College Dublin, Dublin, Ireland
  • Godson, Catherine, The Conway Institute of Biomolecular and Biomedical, Belfield, Dublin, Ireland
  • Belton, Orina, University College Dublin, Dublin, Ireland
  • Crean, John, University College Dublin, Dublin, Ireland

Group or Team Name

  • Diabetes Complications Research Centre, UCD School of Biomolecular and Biomedical Science, University College Dublin

The role of inflammatory cells in chronic kidney disease has been well documented, with macrophage infiltration and accumulation implicated in the initiation and progression of renal injury. However, current models of disease fail to accurately reflect the initial cycles of damage and resolution. At the core of this issue remains a fundamental gap in our knowledge of how discrete inflammatory signalling networks converge and interact with renal tissue to cause fibrosis. We have found that plasticity of resident cells and infiltrating cells is reflected by significantly increased levels of the stemness regulator, miR-302 in exosomes of patients with CKD while additionally the TGFβ signalling network was identified as a mediator of macrophage reprogramming.


IPSCs were differentiated into kidney organoids over a 24 day period. Primitive streak formation was induced by treating cells with CHIR99021 8µM for 3 days. Medium was then changed to APEL medium supplemented with 200ng/ml FGF9 and Heparin 1µg/ml. On day 12, growth factors were removed and organoids were matured until day 24.

Organoids were then cultured in conditioned media from peripheral blood mononuclear cells (PBMCs) polarised towards a pro-inflammatory phenotype using lipopolysaccharide 200ng/ml and Interferon γ 20ng/ml and towards a pro-resolving phenotype using interleukin 4 20ng/ml and interleukin 13 20ng/ml. Organoids were subsequently fixed, stained and imaged using confocal microscopy for known markers of renal damage. Similarly, organoids were also treated with the nephrotoxic agent Aristolochic Acid (AA) and co cultured with PBMCs.


Culturing of organoids in conditioned media for a 48 hour period lead to significant increases in the expression of αSmooth Muscle Actin, Fibronectin and KIM-1. Co culture of organoids exposed to AA for up to 24 hours with PBMCs resulted in significant damage to the organoid, accompanied by migration and infiltration of differentiated cells into these damaged organoids.


We propose that this novel model of macrophage induced renal damage can be used to investigate the role of inflammatory pathways which result in fibrosis and that by manipulating the plasticity of resident and infiltrating cells we may inhibit or reverse the progression of fibrosis in vivo.