Abstract: SA-PO0013
GPX4-Associated Cytoprotective Activity of an Autologous Cell Therapy in Human In Vitro and Ex Vivo CKD Models
Session Information
- Development, Stem Cells, and Regenerative Medicine
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 700 Development, Stem Cells, and Regenerative Medicine
Authors
- Cloer, Caryn M., ProKidney LLC, Morrisville, North Carolina, United States
- Czerwinski, Michael J., ProKidney LLC, Morrisville, North Carolina, United States
- Lillich, Melina, ProKidney LLC, Morrisville, North Carolina, United States
- Conway, Anthony, ProKidney LLC, Morrisville, North Carolina, United States
Background
Rilparencel, an autologous cell therapy containing selected renal cells (SRC) currently in a Phase 3 registrational study (NCT05099770), potentially preserves renal function in patients with advanced CKD and T2D. The mechanisms underlying efficacy, including potential cytoprotective effects within a diseased kidney, remain incompletely defined.
Methods
Human proximal tubular epithelial cells (hRPTEC) were subjected to metabolic and inflammatory stress (IM) to model tubular injury. Glutathione peroxidase 4 (GPX4) activity was pharmacologically modulated using RSL3 (inhibitor) and PKUMDL-LC-101-D04 (1D4, activator). Time-resolved responses were evaluated for oxidative stress (GSH:GSSG, TFCH, BODIPY) and mitochondrial fitness (TMRM, Seahorse bioanalyzer) across control and injury conditions ± SRC ± RSL3 (Fig 1A). Ex vivo human CKD kidney tissue was used to assess transcriptional responses to SRC after 10d.
Results
IM induced early glutathione redox imbalance, preceding lipid peroxidation and mitochondrial dysfunction in hRPTECs. GPX4 modulation altered injury severity, with inhibition exacerbating and activation partially mitigating phenotypes (Fig 1B-D). SRC attenuated injury phenotypes in a GPX4-dependent manner. In extended in vitro cultures, early protective effects translated into a progressive improvement in mitochondrial fitness over 7d (Fig 2A). In ex vivo human CKD kidney tissue, SRC induced bidirectional regulation of canonical Nrf2-responsive gene programs associated with lipid peroxidation repair (Fig 2B).
Conclusion
Collectively, these findings support a role for GPX4-associated regulation of redox balance and mitochondrial function in SRC-mediated cytoprotection, linking early functional improvements observed in vitro with transcriptional changes in ex vivo human CKD tissue.