Kidney organoid systems for studies of immune-mediated kidney diseases: challenges and opportunities

Abstract

Acute and chronic kidney diseases are major contributors to morbidity and mortality in the global population. Many nephropathies are considered to be immune-mediated with dysregulated immune responses playing an important role in the pathogenesis. At present, targeted approaches for many kidney diseases are still lacking, as the underlying mechanisms remain insufficiently understood. With the recent development of organoids-a three-dimensional, multicellular culture system, which recapitulates important aspects of human tissues-new opportunities to investigate interactions between renal cells and immune cells in the pathogenesis of kidney diseases arise. To date, kidney organoid systems, which reflect the structure and closer resemble critical aspects of the organ, have been established. Here, we highlight the recent advances in the development of kidney organoid models, including pluripotent stem cell-derived kidney organoids and primary epithelial cell-based tubuloids. The employment and further required advances of current organoid models are discussed to investigate the role of the immune system in renal tissue development, regeneration, and inflammation to identify targets for the development of novel therapeutic approaches of immune-mediated kidney diseases.

Keywords: Immune cells; Immune cell–epithelial cell interaction; Immune-mediated kidney diseases; Kidney organoids; Tubuloids.

Fig. 1

Kidney anatomy and physiology

Fig. 2

Tubuloids and iPSC-derived kidney organoids: a Urine-derived tubuloids with typical cystic morphology; scale bar: 300 µm. b Immunofluorescence staining of iPSC-derived kidney organoids red: LTL staining = proximal tubular cells, green: Nephrin, blue: Dapi = nuclei; scale bar: 20 µm

Fig. 3

Future approaches for autologous organoid–immune cell co-culture systems