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Abstract: FR-PO374

Generation of Mouse/Human Chimeric Organoids by Renal Fetal Dissociated Cell and Induced Nephron Progenitor Cells

Session Information

Category: Development‚ Stem Cells‚ and Regenerative Medicine

  • 500 Development‚ Stem Cells‚ and Regenerative Medicine

Authors

  • Matsumoto, Naoto, Tokyo Jikeikai Ika Daigaku Igakubu Igakuka, Minato-ku, Tokyo, Japan
  • Yamanaka, Shuichiro, Tokyo Jikeikai Ika Daigaku Igakubu Igakuka, Minato-ku, Tokyo, Japan
  • Matsui, Kenji, Tokyo Jikeikai Ika Daigaku Igakubu Igakuka, Minato-ku, Tokyo, Japan
  • Saito, Yatsumu, Tokyo Jikeikai Ika Daigaku Igakubu Igakuka, Minato-ku, Tokyo, Japan
  • Matsumoto, Kei, Tokyo Jikeikai Ika Daigaku Igakubu Igakuka, Minato-ku, Tokyo, Japan
  • Kobayashi, Eiji, Tokyo Jikeikai Ika Daigaku Igakubu Igakuka, Minato-ku, Tokyo, Japan
  • Yokoo, Takashi, Tokyo Jikeikai Ika Daigaku Igakubu Igakuka, Minato-ku, Tokyo, Japan
Background

Several aspects of renal development are still unclear. Consequently, not all component cells of the kidney can be made from induced pluripotent stem cells (iPSCs). For example, human stromal progenitor cells cannot be artificially produced. Thus generating a completely functional kidney from iPSCs is still difficult. Hence attempts have been made to compensate for this limitation using xenogeneic cells.
Renal progenitor cells self-organize into nephrons by aggregation. We hypothesized that taking advantage of this reaggregation mechanism, high concentration of human nephron progenitor cells (NPCs) and low of mouse dissociated single cells (DSCs) could increase cell to cell the contact chance efficiently for generating chimeric nephrons. Therefore, we examined whether higher-order chimeric structures could be obtained by mixing human NPCs with mouse renal progenitor cells to generate heterologous renal chimeric organoids.

Methods

NPCs were selectively induced from human iPSCs using the method reported by Taguchi and Nishinakamura et al., and spheres were created by mixing the induced NPCs with renal progenitor cells extracted from B6 mice kidneys at E13.5 and at a 1:3 ratio. The combined cells were cultured with spinal cord cells in Transwell plates. The resulting tissue was collected on day 6 and histological evaluation of differentiation was performed by immunostaining.

Results

On day 6, human NPCs aggregated on mouse ureteric bud (UB) tips and exhibited a chimeric CM structure. All NPCs were derived from human cells, and all UB tips were derived from mouse cells. The spinal cord cocultures revealed human-derived distal tubules (DTs), which were derived exclusively from human cells, connected to mouse collecting ducts (CDs).

Conclusion

Using NPCs derived from human iPSCs, we have successfully generated higher-order interspecies renal chimeric organoids with connected human CM and mouse tubular structures. This new chimeric organoid is expected to provide new insights into induced renal cells and contribute substantially to the production of kidneys for regenerative medicine.

Funding

  • Government Support – Non-U.S.