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In vivo regeneration of interspecies chimeric kidneys using a nephron progenitor cell replacement system.
Fujimoto, Toshinari; Yamanaka, Shuichiro; Tajiri, Susumu; Takamura, Tsuyoshi; Saito, Yatsumu; Matsumoto, Kei; Takase, Kentaro; Fukunaga, Shohei; Okano, Hirotaka James; Yokoo, Takashi.
Afiliación
  • Fujimoto T; Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Yamanaka S; Division of Regenerative Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Tajiri S; Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Takamura T; Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Saito Y; Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Matsumoto K; Division of Regenerative Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Takase K; Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Fukunaga S; Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Okano HJ; Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
  • Yokoo T; Division of Cardiology and Nephrology, Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Shimane, 693-8501, Japan.
Sci Rep ; 9(1): 6965, 2019 05 06.
Article en En | MEDLINE | ID: mdl-31061458
Kidney regeneration is expected to be a new alternative treatment to the currently limited treatments for chronic kidney disease. By transplanting exogeneous nephron progenitor cells (NPCs) into the metanephric mesenchyme of a xenogeneic foetus, we aimed to regenerate neo-kidneys that originate from transplanted NPCs. Previously, we generated a transgenic mouse model enabling drug-induced ablation of NPCs (the Six2-iDTR mouse). We demonstrated that eliminating existing native host NPCs allowed their 100% replacement with donor mouse or rat NPCs, which could generate neo-nephrons on a culture dish. To apply this method to humans in the future, we examined the possibility of the in vivo regeneration of nephrons between different species via NPC replacement. We injected NPCs-containing rat renal progenitor cells and diphtheria toxin below the renal capsule of E13.5 metanephroi (MNs) of Six2-iDTR mice; the injected MNs were then transplanted into recipient rats treated with immunosuppressants. Consequently, we successfully regenerated rat/mouse chimeric kidneys in recipient rats receiving the optimal immunosuppressive therapy. We revealed a functional connection between the neo-glomeruli and host vessels and proper neo-glomeruli filtration. In conclusion, we successfully regenerated interspecies kidneys in vivo that acquired a vascular system. This novel strategy may represent an effective method for human kidney regeneration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regeneración / Células Madre / Trasplante de Células Madre / Organogénesis / Riñón / Mesodermo / Nefronas Límite: Animals Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regeneración / Células Madre / Trasplante de Células Madre / Organogénesis / Riñón / Mesodermo / Nefronas Límite: Animals Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido