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Kidney organoids as models for hereditary kidney diseases: Toward precision medicine (Review)
Sheng Cui1, Tianlei Chen1, Yun Zou1
1Department of Nephrology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China.
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.
Insights
Kidney organoids derived from human induced pluripotent stem cells (hiPSCs) offer a powerful platform for studying chronic kidney disease (CKD) and testing new therapies. Advances enable better modeling of kidney development and disease, though challenges remain for complex applications.
Area of Science:
- Regenerative Medicine
- Stem Cell Biology
- Nephrology Research
Background:
- Chronic kidney disease (CKD) is a global health issue requiring novel therapeutic strategies.
- Kidney organoids are valuable tools for modeling human kidney development and disease in vitro.
- Human induced pluripotent stem cells (hiPSCs) and 3D organ culture advancements facilitate kidney organoid development.
Purpose of the Study:
- To review the application of hiPSC-derived 3D kidney organoids in CKD research.
- To discuss current limitations in organoid culture methods for kidney disease modeling.
- To examine the role of CRISPR/Cas9 technology and explore future research directions.
Main Methods:
- Utilizing hiPSCs to generate renal cell lineages and kidney organoids.
- Employing advanced 3D organ culture techniques for in vitro kidney development modeling.
- Applying patient-derived or genetically edited organoids to model specific kidney diseases.
Main Results:
- Established protocols allow generation of renal cell lineages, including ureteric bud and collecting ducts.
- Kidney organoids successfully model genetic kidney diseases like polycystic kidney disease.
- Generated kidney tissues closely mimic the morphology of native human kidneys.
Conclusions:
- hiPSC-derived kidney organoids are crucial for mechanism-based therapeutics in CKD.
- Current organoid models face challenges in complex disease modeling and generating transplantable organs.
- CRISPR/Cas9 technology and ongoing research hold promise for advancing kidney organoid applications.
