Abstract: TH-PO0553
Urine-Derived Stem Cell Extracellular Vesicles Promote Recovery from AKI in Mice and Human Kidney Organoids
Session Information
- Development, Stem Cells, and Regenerative Medicine
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 600 Development, Stem Cells, and Regenerative Medicine
Authors
- Qian, Eddie, Tufts University School of Medicine, Boston, Massachusetts, United States
- Bejoy, Julie, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Welch, Richard C., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Farry, Justin M., Vanderbilt University, Nashville, Tennessee, United States
- Hartert, Jack, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Cartailler, Jean-Philippe, Vanderbilt Center for Stem Cell Biology, Nashville, Tennessee, United States
- Gibson-Corley, Katherine N, Department of Medicine, Division of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Wilson, Matthew H., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Woodard, Lauren Elizabeth, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
Extracellular vesicles (EVs) contain RNA, protein, and lipids from their parental cell type, which led to the hypothesis that urine-derived stem cell EVs (USC-EVs) could have regenerative effects for acute kidney injury (AKI). Current AKI treatments support recovery but are not curative. As such, new therapeutics for renal regeneration are needed. Here, we tested if treatment of USC-EVs could improve cell viability and reverse injury incurred by nephrotoxic insult in both traditional in vitro and organoid models of AKI. We also evaluated USC-EVs in promoting AKI recovery of AKI in a unilateral nephrectomy and ischemia reperfusion injury (UNIRI) mouse model. Finally, to understand the possible mechanism of USC-EVs during injury, we analyzed miRNA contents and verified target overexpression in our models.
Methods
EVs were tested in the proximal tubule epithelial cell line HK-2 and human iPSC-derived kidney organoids cultured using the Takasato protocol. In vitro nephrotoxicity was induced using cisplatin. Cell viability, cytotoxicity and oxidative damage were measured using fluorometric and colorimetric assays. Ki-67 expression of proliferation was tested using immunostaining. Tubule organoid architecture was visualized using the marker LTL. Renal injury was recapitulated in vivo using UNIRI, with USC-EV tail vein injection as treatment. Mice were tested for histologic changes, injury markers, and kidney function. Multi-MicroRNA analysis was conducted in USC-EVs.
Results
USC-EV treatment increased cellular proliferation, decreased cytotoxicity, and lowered mitochondrial oxidative stress compared to injury groups. In UNIRI, USC-EVs improved pathology and reduced the injury marker KIM-1. miRNA sequencing revealed USC-EVs contain miRNAs that target epithelial cell proliferation and positive regulation of the MAPK pathway.
Conclusion
USC-EVs reduce mitochondrial ROS and subsequent damage to cellular membrane integrity by activating anti-oxidative enzymes. USC-EVs promote proliferation predominantly in proximal tubules both in the presence and absence of injury. This is due to cargo miRNAs that upregulate MAPK signaling. Our results suggest that USC-EVs have therapeutic potential for the treatment of AKI and other kidney diseases.
Funding
- Other NIH Support