Kidney Organoids as Disease Models: Strengths, Weaknesses and Perspectives

Abstract

Chronic kidney disease is a major global health problem, as it affects 10% of the global population and kills millions of patients every year. It is therefore of the utmost importance to develop models that can help us to understand the pathogenesis of CKD and improve our therapeutic strategies. The discovery of human induced pluripotent stem cells (hiPSCs) and, more recently, the development of methods for the generation of 3D organoids, have opened the way for modeling human kidney development and disease in vitro , and testing new drugs directly on human tissue. In this review we will discuss the most recent advances in the field of kidney organoids for modeling disease, as well as the prospective applications of these models for drug screening. We will also emphasize the impact of CRISPR/cas9 genome engineering on the field, point out the current limitations of the existing organoid technologies, and discuss a set of technical developments that may help to overcome limitations and facilitate the incorporation of these exciting tools into basic biomedical research.

Kidney organoids recapitulate human basement membrane assembly in health and disease

“…Despite the developmental limitations with iPSC-derived kidney organoids, including lack of directional cues, vascularization, and cortical-medullary segmentation (Romero-Guevara et al, 2020), this system has morphological and molecular features comparable to fetal kidney tissue that overcome species differences and provides a complex in vitro environment to examine BM assembly (Bantounas et al, 2018). We demonstrated that kidney organoids differentiate into glomerular structures containing the cells required for GBM assembly and single-cell transcriptomic studies have also shown over 20 other distinct cell populations in kidney organoids (Combes et al, 2019a;Wu et al, 2018).…”

Urine-Derived Epithelial Cells as Models for Genetic Kidney Diseases

“…Co-culture techniques have been successfully applied to mimic specific tissues. In 2011, Slater et al used the co-culturing method to generate a functional tri-layer in vitro model of the glomerular filtration barrier, comprising podocytes and glomerular epithelial cells on an artificial membrane [118].…”

The Nephrotoxin Puromycin Aminonucleoside Induces Injury in Kidney Organoids Differentiated from Induced Pluripotent Stem Cells

“…Besides improving rodent models, the establishment of pluripotent stem-cell-based kidney cells in 2D or 3D organoids holds great potential for gaining further insights into disease mechanisms and potential therapies [ 12 ]. Recent studies have suggested using primary kidney cells for the generation of kidney organoids as an alternative to pluripotent stem cells [ 13 , 14 , 15 ].…”