Abstract: TH-PO0370
Engineered Podocyte-Targeted Extracellular Vesicle Therapy: A New Strategy for CKD
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Dedhia, Charmi, Children's Hospital Los Angeles, Los Angeles, California, United States
- Huang, Yi, University of Southern California, Los Angeles, California, United States
- Da Sacco, Stefano, Children's Hospital Los Angeles, Los Angeles, California, United States
- Chung, Eun ji, University of Southern California, Los Angeles, California, United States
- Perin, Laura, Children's Hospital Los Angeles, Los Angeles, California, United States
Background
Loss of podocytes is the culprit of most progressive glomerulopathies. Standard treatments for chronic kidney disease (CKD) are not designed to specifically restore podocyte function. There is a critical unmet need for new, more effective podocyte-based therapeutic strategies. We showed that amniotic fluid stem cells’ extracellular vesicles (hAFSC-EVs) present with renal disease-modifying activity. To advance CKD treatments with enhanced podocyte therapeutic efficacy while minimizing off-target effects, we investigated a delivery strategy by engineering podocyte-targeted EVs.
Methods
We designed a specific podocyte-specific peptide (PSP), generating PSP-EVs, and characterized them using TEM, NTA, and NanoSight NS300. Targeting efficiency was evaluated using DiO-labeled EVs in human primary podocytes, followed by fluorescence microscopy and ImageJ quantification. Multi-cell-type uptake studies were performed using the IncuCyte system in human kidney cell types. Functional assessment was conducted using a glomerulus-on-a-chip (GOAC) model under puromycin aminonucleoside (PAN)-induced injury. In vivo biodistribution was assessed in Alport syndrome mice, our model of CKD, with DiR-labeled EVs, and organ imaging ex vivo, followed by the disease-modifying activity of PSP-EVs vs non-targeting EVs (NT-EVs).
Results
TEM confirmed uniform morphology and monodisperse size of PSP-EVs. These EVs exhibited an average size of 183.2 ± 2.0 nm. In vitro studies demonstrated significantly higher uptake of PSP-EVs in human primary podocytes compared to NT-EVs. Time-course and multi-cell-type analyses showed preferential podocytes uptake of PSP-EVs relative to other renal cell types (glomerular endothelial cells, mesangial cells, and proximal tubular cells). In the GOAC model, PSP-EVs improved functional readouts under PAN-induced injury conditions vs NT-EVs. In vivo, PSP-EVs selectively localized to the kidneys (podocytes) post-injection vs NT-EVs and lower proteinuria.
Conclusion
We demonstrated that our peptide does not alter the morphology of our EVs. Importantly, PSP-EVs enhanced specificity for podocytes in vitro and in vivo, with improved functional outcomes in a kidney injury model. These findings support PSP-EVs as a promising platform for podocyte-targeted therapeutic delivery in glomerular diseases.