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Updated: Jul 30, 2026
Early Detection of Drug-Induced Renal Hemodynamic Dysfunction Using Sonographic Technology in Rats
Published on: March 11, 2016
Long-term viable chimeric nephrons generated from progenitor cells are a reliable model in cisplatin-induced toxicity
Kenji Matsui1, Shuichiro Yamanaka2, Sandy Chen1
1Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.
Abstract:
Kidney organoids have shown promise as evaluation tools, but their in vitro maturity remains limited. Transplantation into adult mice has aided in maturation; however, their lack of urinary tract connection limits long-term viability. Thus, long-term viable generated nephrons have not been demonstrated. In this study, we present an approachable method in which mouse and rat renal progenitor cells are injected into the developing kidneys of neonatal mice, resulting in the generation of chimeric nephrons integrated with the host urinary tracts. These chimeric nephrons exhibit similar maturation to the host nephrons, long-term viability with excretion and reabsorption functions, and cisplatin-induced renal injury in both acute and chronic phases, as confirmed by single-cell RNA-sequencing. Additionally, induced human nephron progenitor cells differentiate into nephrons within the neonatal kidneys. Collectively, neonatal injection represents a promising approach for in vivo nephron generation, with potential applications in kidney regeneration, drug screening, and pathological analysis.
Insights
Neonatal injection of renal progenitor cells generates chimeric nephrons integrated with host urinary tracts, enabling long-term viability and function. This method offers a promising approach for kidney regeneration and drug screening.
Area of Science:
- Regenerative Medicine
- Developmental Biology
- Nephrology
Background:
- Kidney organoids show limited in vitro maturity and lack urinary tract integration for long-term viability.
- Previous transplantation methods into adult mice have not achieved long-term viable generated nephrons due to lack of integration.
- Demonstrating long-term viable, functional nephrons is crucial for advancing kidney research and therapies.
Purpose of the Study:
- To develop an approachable method for generating long-term viable, functional nephrons in vivo.
- To investigate the integration and maturation of xenografted renal progenitor cells within a host kidney.
- To establish a model for studying kidney injury and regeneration.
Main Methods:
- Injection of mouse and rat renal progenitor cells into neonatal mouse kidneys.
- Generation of chimeric nephrons with integration into the host urinary tract.
- Assessment of nephron maturation, viability, function (excretion/reabsorption), and response to cisplatin-induced injury using single-cell RNA-sequencing.
Main Results:
- Successfully generated chimeric nephrons integrated with host urinary tracts.
- Chimeric nephrons demonstrated similar maturation to host nephrons and long-term viability.
- Functional excretion and reabsorption capabilities were observed, along with responses to acute and chronic cisplatin injury.
- Human nephron progenitor cells also differentiated into nephrons within neonatal kidneys.
Conclusions:
- Neonatal injection of renal progenitor cells is a promising approach for in vivo nephron generation.
- This method facilitates long-term viability and functional integration of generated nephrons.
- Potential applications include kidney regeneration, drug screening, and pathological analysis.
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