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Abstract: FR-PO394

Selected Renal Cells Self-Organize to Form Neo-Nephrons and Attenuate Kidney Disease

Session Information

Category: Development‚ Stem Cells‚ and Regenerative Medicine

  • 500 Development‚ Stem Cells‚ and Regenerative Medicine

Authors

  • Narayan, Prakash, ProKidney, Winston-Salem, North Carolina, United States
  • Rivera, Elias A., Infinium Pathology Consultants, Oak Ridge, North Carolina, United States
  • Jain, Deepak, ProKidney, Winston-Salem, North Carolina, United States
  • Bertram, Tim A., ProKidney, Winston-Salem, North Carolina, United States
  • Ludlow, John W., ProKidney, Winston-Salem, North Carolina, United States
  • Basu, Joydeep, ProKidney, Winston-Salem, North Carolina, United States
Background

Selected renal cells (SRC), a renal epithelial cell-enriched platform, is being advanced as autologous cell-based therapy for treatment of chronic kidney disease (CKD). In the present study, we tested the hypothesis that SRC forms organoids which self-organize into neo-nephrons, and its implantation into the diseased kidney induces repair and ameliorates organ dysfunction.

Methods

Rodent and human SRC were generated from kidney tissue using buoyant density gradient centrifugation. SRC cultures ± hydrogel were examined using light and immunofluorescence microscopy. SRC retention in vivo and bioactivity were examined in rodent models of CKD (ZSF1 rat and subtotal nephrectomy).

Results

In culture, both rodent and human SRC formed organoids (Figure 1A) that expressed renal markers including the Na-K-2Cl cotransporter, gamma-glutamyltransferase type I, megalin, and cubilin. In the presence of hydrogel, these SRC-derived organoids self-organized into tubules (Figure 1B), and other neo-nephron structures. Seeding SRC into diseased kidneys resulted in its incorporation into the renal parenchyma, evident even 4 months post-implantation, and formation of glomerular capillary loops and neo-nephrons. In subtotal nephrectomized rats, SRC implantation was associated with improvement in both survival and renal function (BUN, SCr, UPCr; p<0.05 vs. sham).

Conclusion

SRC forms organoids that express renal markers, and in the presence of hydrogel, self-organize into neo-nephrons. When introduced into diseased kidneys SRC exhibits reparative and restorative activity inducing neo-nephrogenesis, and improving survival and renal filtration. SRC-based Renal Autologous Cell Therapy (REACT) is in late-stage clinical trials for CKD, and has been granted Regenerative Medicine Advanced Therapy designation by Food and Drug Administration.

Figure 1. Organoids (A, arrows, 20X) formed from cultured SRC self-organize into tubules and neo-nephrons (B, arrow, 20X) in the presence of hydrogel.

Funding

  • Commercial Support