Abstract: SA-PO549
Regeneration of Rat Nephrons in the Mouse Metanephros: In Vivo Regeneration of Nephrons between Different Species under the Administration of Optimal Immunosuppressive Agents
Session Information
- Developmental Biology
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Developmental Biology and Inherited Kidney Diseases
- 401 Developmental Biology
Authors
- Fujimoto, Toshinari, Jikei University School of Medicine, Tokyo, Japan
- Yamanaka, Shuichiro, Jikei University School of Medicine, Tokyo, Japan
- Tajiri, Susumu, Jikei University School of Medicine, Tokyo, Japan
- Matsumoto, Kei, Jikei University School of Medicine, Tokyo, Japan
- Fukunaga, Shohei, Jikei University School of Medicine, Tokyo, Japan
- Yokoo, Takashi, Jikei University School of Medicine, Tokyo, Japan
Background
The transplant of exogenous nephron progenitor cells（NPCs）to a nephrogenic niche has demonstrated very low engraftment efficiency, possibly due to the competition with existing native host NPCs occupying the niche. Previously, we generated a transgenic mouse model with ablation of NPCs by using a drug for induction. We demonstrated that host mouse NPCs were replaced with donor mouse NPCs by eliminating existing native host NPCs, and that donor cells regenerate neo nephrons that connect with host collecting ducts. In the future, we aim to regenerate human nephrons in different species using the NPCs elimination and replacement system, and apply this novel strategy to the treatment of kidney failure. As a first step, we needed to examine the possibility of interspecies regeneration of nephrons. We already succeeded in regenerating rat nephrons in the mouse metanephros（MN）on an organ culture dish using this system. In this work, we verified the in vivo regeneration of nephrons between rat and mouse models.
Methods
In the transgenic mouse, diphtheria toxin receptor is specifically expressed on Six2-positive NPCs. The MN was isolated from the E13 embryo, following which donor rat NPCs that were not affected by the diphtheria toxin were transplanted into the MN. Diphtheria toxin was simultaneously added to the MN for the elimination of native NPCs only. Subsequently, the mouse MN-implanted rat NPCs were transplanted into the abdominal para-aortic area of an adult rat under the administration of tacrolimus and Mycophenolate mofetil. After 3 weeks, regeneration of rat nephrons in the transplanted mouse MN was examined through immunohistological analysis.
Results
Donor rat NPCs were noted engraftment in the host mouse cap mesenchyme, which ablated native NPCs using diphtheria toxin. Additionally, donor rat NPCs differentiated into neo nephrons in the host mouse metanephros transplanted into the adult rat.
Conclusion
We demonstrated interspecies regeneration of nephrons within a living organism under the administration of optimal immunosuppressive agents by using the NPCs elimination and replacement system. This novel strategy is considered an effective method for kidney regeneration.