Long-term viable chimeric nephrons generated from progenitor cells are a reliable model in cisplatin-induced toxicity

Autor: Kenji Matsui, Shuichiro Yamanaka, Sandy Chen, Naoto Matsumoto, Keita Morimoto, Yoshitaka Kinoshita, Yuka Inage, Yatsumu Saito, Tsuyoshi Takamura, Toshinari Fujimoto, Susumu Tajiri, Kei Matsumoto, Eiji Kobayashi, Takashi Yokoo
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Communications Biology, Vol 6, Iss 1, Pp 1-15 (2023)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-023-05484-9
Popis: 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.
Databáze: Directory of Open Access Journals
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