Kidney Week

Abstract: TH-OR134

Exo Utero Method to Regenerate Nephrons from Nephron Progenitor Cells in the Living Fetus

Session Information

• Translational Research Innovations in Kidney Organoid and Bioengineered Model Systems
  October 25, 2018 | Location: 4, San Diego Convention Center
  Abstract Time: 05:06 PM - 05:18 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

• Yamanaka, Shuichiro, The Jikei University School of Medicine,Tokyo,Japan, Tokyo, Japan

Shuichiro Yamanaka, MD, PhD

• Saito, Yatsumu, The Jikei University School of Medicine,Tokyo,Japan, Tokyo, Japan

Yatsumu Saito,

• Takamura, Tsuyoshi, The Jikei University School of Medicine,Tokyo,Japan, Tokyo, Japan

Tsuyoshi Takamura,

• Fujimoto, Toshinari, The Jikei University School of Medicine,Tokyo,Japan, Tokyo, Japan

Toshinari Fujimoto,

• Tajiri, Susumu, The Jikei University School of Medicine, Tokyo, Japan., Minato-ku, ToKyo, Japan

Susumu Tajiri,

• Matsumoto, Kei, The Jikei University School of Medicine, Tokyo, Japan

Kei Matsumoto,

• Yokoo, Takashi, The Jikei University School of Medicine,Tokyo,Japan, Tokyo, Japan

Takashi Yokoo,

Background

Kidney regeneration using native kidney development has been previously reported. We previously reported that neonephrons could be generated by transplanting nephron progenitor cells (NPCs) into the nephrogenic zone in mice and replacing exogenous cells with host cells. In this cell replacement method, the fetal kidney was used as a scaffold for regeneration. We postulated that direct transplantation of NPCs into the scaffold in utero may obtain a more suitable developmental environment for kidney regeneration. We tried an exo utero method for kidney regeneration was used to examine whether NPCs could be transplanted into the retroperitoneum near the fetal host kidney without fetal sacrifice in vivo, and the development of neonephrons was examined.

Methods

Using an exo utero method to dissect only the myometrial layer of the mouse fetus which has only one clear amnion, cells can be injected to the fetus in utero. This approach allows the fetus in the amniotic membrane to be returned to the uterus after cell transplantation. An exo utero method was used to transplant GFP-expressing NPCs into the retroperitoneum on E13.5. After cell transplantation, the fetus continued to develop in the mother’s uterus for 6 days. Following cesarean section on E19.5, histopathological examination was performed to determine NPC differentiation into nephrons. To determine whether cell transplantation in the fetus had a negative effect on fetal growth, fetal body weight and crown-rump-length (CRL) were measured on E19 and compared with those of fetuses who did not receive NPC transplantation.

Results

Glomeruli derived from transplanted NPCs expressed the nephron differentiation markers podocin, nephrin, megalin and aquaporin 1. CD31-positive blood vessels were observed inside the glomeruli. There were no significant differences in body weight or CRL between the fetuses with and without NPC transplantation.

Conclusion

Transplantation of exogenous NPCs into the retroperitoneum using an exo utero method could differentiate into nephrons in vivo. This method, which did not adversely affect fetal growth, is potentially applicable to kidney regeneration using NPCs.

Funding

• Government Support - Non-U.S.