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Abstract: FR-PO759

Optimal Generation of Mesangial Cells and the Stromal Progenitor Cell Lineage from a Platelet-Derived Growth Factor Receptor Alpha Fraction of Fetus Cells

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Saito, Yatsumu, The Jikei University School of Medicine, Tokyo, Japan
  • Yamanaka, Shuichiro, The Jikei University School of Medicine, Tokyo, Japan
  • Takamura, Tsuyoshi, The Jikei University School of Medicine, Tokyo, Japan
  • Fujimoto, Toshinari, The Jikei University School of Medicine, Tokyo, Japan
  • Tajiri, Susumu, The Jikei University School of Medicine, Tokyo, Japan
  • Matsumoto, Kei, The Jikei University School of Medicine, Tokyo, Japan
  • Yokoo, Takashi, The Jikei University School of Medicine, Tokyo, Japan
Background

We previously transplanted a cell population comprising several heterogenic types of renal progenitor cells (RPCs) from mouse metanephros into the nephrogenic zone of other mouse metanephros and regenerated nephrons derived from the transplanted RPCs. However, mesangial cells of the regenerated glomeruli comprised cells derived from the host. We could not confirm the regeneration of mesangial cells by the transplanted cells. Therefore, we optimized the RPC cell composition via cell sorting and examined the possibility of regenerating the mesangial cells.

Methods

Metanephros was harvested from GFP mice, and an enzymatic treatment extracted the dissociated single cells (DSCs) from the metanephros. Stromal progenitor cell components were extracted via cell sorting by targeting the platelet-derived growth factor receptor alpha (PDGFRa) fraction from the DSCs. Three groups of cells, i.e., the PDGFRa-sorted cells, non-sorted cells, and fibroblasts as controls, were transplanted into the nephrogenic zone of B6 mice metanephros. Then, these groups were transplanted under the retroperitoneum of the para-aortic region of adult B6 mice and harvested after 2 weeks. Specimens were assessed via immunofluorescence staining. Furthermore, the regenerative cells were counted to the extent to which the transplanted cells reached.

Results

In the fibroblast group, the cells transplanted to the nephrogenic zone did not colonized in the metanephros. In the non-sorted group, although some cells colonized, there was negligible regeneration of the mesangial cells. However, in the PDGFRa-fraction sorted group, we confirmed regeneration of the mesangial cells from the exogenous cells in 92% of glomeruli (n=13). Furthermore, the proportion of the exogenous mesangial cells with a single glomerulus unit was 67.5%. We also confirmed regeneration of other stromal progenitor cell lineages, such as interstitial fibroblasts, vascular pericytes, and juxtaglomerular cells.

Conclusion

When we increased the ratio of the stromal progenitor cells via cell sorting targeting the PDGFRa fraction from DSCs, we succeeded in efficiently regenerating the mesangial cells and other stromal progenitor cell lineages, such as interstitial fibroblasts, pericytes, and juxtaglomerular cells, in the kidney of the mouse embryos.