Jul 2026· Experimental and Therapeutic Medicine· Vol 32, pp. 1-15· 0 citations· 123 references
Medicine
TL;DR
The application of hiPSC-derived 3D organoids in CKD research is discussed and the limitations of current organ culture methods are addressed, the impact of CRISPR/Cas9 technology is examined, and potential future directions are investigated.
Abstract
Kidney organoids are important tools for modeling human development and disease, especially in chronic kidney disease (CKD), which is a global health challenge. Current treatment strategies focus on delaying disease progression by managing underlying causes, and in this regard, kidney organoids offer a platform for mechanism-based therapeutics. Advances in the understanding of human induced pluripotent stem cells (hiPSCs) and sophisticated 3D organ culture methods have enabled researchers to replicate human kidney development and disease mechanisms in vitro, thereby opening new avenues for drug testing. Although the methods for generating renal cell lineages are well established, new protocols for inducing lineages, such as the ureteric bud and collecting ducts, have emerged over the past 5 years. Patient-derived or genetically edited kidney organoids have been used to successfully model various genetic kidney diseases, notably polycystic kidney disease, and to generate kidney tissues that closely mimic the morphology of real organs. However, achieving more complex disease modeling and generating transplantable synthetic kidneys still has notable challenges. The present review discusses the application of hiPSC-derived 3D organoids in CKD research and addresses the limitations of current organ culture methods. The present review also examines the impact of CRISPR/Cas9 technology, and investigates potential future directions.
Polycystic kidney disease (PKD) is commonly inherited as a loss-of-function mutation in PC1 (polycystin-1) or PC2. The molecular functions of polycystins remain uncertain, and therapeutics remain limited for millions of patients. One major roadblock has been the scarcity of assays that re-create PKD-specific cystogenesis in vitro, to complement mouse models. Over the past decade, a human organoid model of PKD has emerged that promises to bridge this gap. Human kidney organoids derived from PKD1-/- or PKD2-/- pluripotent stem cells recapitulate the pathognomonic cystic phenotype in a PKD-specific manner. This system reveals that PKD cystogenesis is a cell intrinsic process that can be re-created in vitro. Human PKD organoids have revealed unexpected mechanisms for PKD cystogenesis, and have been utilized to blueprint new therapeutic strategies, but their potential is not yet fully realized. The complexity and cost of organoids remain significant barriers to entry, and dedicated technology development is required to improve their physiological relevance. Here we review important achievements, current limitations, and future strategies, with a focus on translational 'bench to bedside' potential of PKD organoids as drug development tools.
Hongxia Fu, Benjamin S. Freedman· Nephron· 0 citations
This review systematically summarizes the roles of various stem cells in angiogenesis, outlines strategies for constructing vascularized organoids, and highlights their emerging applications in modeling vascular-associated diseases and regenerative therapy, providing a comprehensive reference for advancing both basic research and clinical translation in vascular medicine.
Qiuyue Gao, Cai-Feng Long, Anjun Zhong et al.· Global Translational Medicin...· 0 citations
This review systematically summarises current fabrication strategies, disease‐modelling utilities and regenerative potentials of liver organoids, alongside the major challenges and future directions.
Tiepeng Wang, Xiaotian Qu, Jinhong Si et al.· Cell Proliferation· 0 citations
This review examines emerging mechanisms that govern kidney fibrogenesis, with emphasis on therapeutic tractability, and considers how experimental models can improve target prioritization and drug development, and summarizes repurposed drugs, pathway-targeted agents, receptor-directed strategies and cell-based approaches under preclinical or clinical evaluation.
Organoids, three-dimensional cell culture models derived from patient tissues or stem cells, have emerged as a cutting-edge technology in personalized medicine, owing to their remarkable ability to closely recapitulate
in vivo
tissue architecture and function. This review provides a comprehensive overview of the technological evolution and construction methodologies of organoids, highlighting their significant applications in oncology, genetic disorders, infectious diseases, and drug screening. This review examines how organoids enable precision medicine by preserving genomic fidelity, predicting drug sensitivity, and creating disease models via gene editing. Despite these advances, organoid technology faces several technical challenges that impede its full clinical translation. Addressing these obstacles is critical for realizing the potential of organoids in individualized therapeutic strategies. This article aims to delineate current progress and future directions in organoid research, furnishing a theoretical foundation and guiding future investigations towards enhancing personalized treatment paradigms.
Xin-Kui Zhou, Xingxue Yan, Zheng-Yang Zhang et al.· Frontiers in Cell and Develo...· 0 citations
