Abstract: SA-PO0763
Urine-Derived Stem Cells Mitigate Podocyte Injury via Antisenescent Mechanisms in Adriamycin-Induced CKD
Session Information
- Glomerular Diseases: Profiling Through Multiomics
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Choi, Dae Eun, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
- Park, Kyungho, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
- Lee, Eu Jin, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
- Ham, Youngrok, Chungnam National University School of Medicine, Daejeon, Korea (the Republic of)
- Kim, Hae Ri, Chungnam National University Sejong Hospital, Sejong, Korea (the Republic of)
- Park, Heewon, Chungnam National University Sejong Hospital, Sejong, Korea (the Republic of)
Background
Podocyte injury plays a pivotal role in the pathogenesis of chronic kidney disease (CKD), leading to progressive glomerulosclerosis and renal dysfunction. Urine-derived stem cells (UDSCs) have emerged as a promising therapeutic modality due to their kidney-origin, non-invasive accessibility, and regenerative potential.
Methods
This study employed an adriamycin (ADR)-induced podocyte apoptosis model using conditionally immortalized human podocytes (CIHP-1) and an ADR-induced CKD mouse model. UDSCs were characterized by mesenchymal and renal progenitor markers and assessed for their multilineage differentiation capacity. In vitro co-culture experiments evaluated UDSC-mediated protection of ADR-treated podocytes via Western blotting and immunofluorescence. In vivo, the therapeutic efficacy of single and repeated UDSC administration was compared. Renal functional markers, histopathology, and podocyte-specific protein expression were examined. Transcriptomic analyses, including differential expression and GSEA, were performed to identify molecular pathways modulated by UDSC therapy.
Results
UDSC co-culture suppressed inflammatory (NF-κB, NLRP3, IL-1β) and apoptotic (p53, cytochrome c, cleaved caspase-3) signaling, while preserving nephrin and actin filament organization in injured podocytes. In vivo, both UDSC treatment strategies improved renal function and histological damage, with repeated dosing showing superior restoration of synaptopodin and α-actinin-4. RNA sequencing revealed that repeated UDSC therapy (ADR_HM) induced broader suppression of ferroptosis, ribosomal biosynthesis, oxidative phosphorylation, and senescence-associated secretory phenotype (SASP) pathways compared to single-dose therapy (ADR_HS). Senescence regulators (Cdkn2a, Trp53) and SASP effectors (Tnf, Il6, Mmp9, Egf) were significantly downregulated in the ADR_HM group.
Conclusion
UDSCs protect against ADR-induced podocyte injury through anti-inflammatory, anti-apoptotic, and anti-senescent mechanisms. Repeated UDSC administration confers enhanced therapeutic efficacy by promoting durable transcriptomic reprogramming and senescence suppression. These findings support the translational potential of UDSCs as a next-generation cell therapy for CKD.