Kidney Organoids: Emerging Models for Kidney Fibrosis—From Current Advances to Experimental Insights
TL;DR
Experimental models of renal fibrosis, kidney organoid generation and characterization, organoid-based fibrosis modeling, and future strategies to improve their translational value are summarized.
Abstract
Chronic kidney disease is a major global health burden, and renal fibrosis represents the common pathological endpoint of progressive kidney injury. Fibrosis is driven by complex interactions among injured epithelial cells, activated fibroblasts, endothelial cells, immune cells, and the extracellular matrix, ultimately leading to irreversible loss of renal function. Although animal models and conventional two-dimensional cell cultures have advanced our understanding of fibrogenic mechanisms, their limited human relevance and physiological complexity restrict translational application. Human pluripotent-stem-cell-derived kidney organoids have emerged as promising three-dimensional models that partially recapitulate renal development, nephron-like organization, and multicellular composition. Recent studies have applied kidney organoids to model renal injury and fibrotic remodeling induced by cytokines, hypoxia, nephrotoxins, genetic defects, and metabolic stress. These systems enable investigation of epithelial damage, inflammatory signaling, fibroblast activation, extracellular matrix deposition, and therapeutic responses in a human cellular context. However, current models remain limited by developmental immaturity, incomplete vascularization, lack of urinary drainage, protocol variability, and simplified fibrosis induction. This review summarizes experimental models of renal fibrosis, kidney organoid generation and characterization, organoid-based fibrosis modeling, and future strategies to improve their translational value.