Kidney Week

Abstract: TH-PO036

Urine-Derived Stem Cells Display Homing, Incorporation, and Repair in Human Organoid and Mouse Models of AKI

Session Information

• AKI: Epidemiology, Risk Factors, and Prevention - 1
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

• Bejoy, Julie, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Julie Bejoy, PhD

• Welch, Richard C., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Richard C. Welch

• Qian, Eddie, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Eddie Qian

• Williams, Felisha M., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Felisha M. Williams, MS

• Wilson, Matthew H., Vanderbilt University Medical Center, Nashville, Tennessee, United States

Matthew H. Wilson, MD, PhD

• Paragas, Neal, University of Washington, Seattle, Washington, United States

Neal Paragas, PhD

• Woodard, Lauren Elizabeth, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Lauren Elizabeth Woodard, PhD

Group or Team Name

• Woodard Lab.

Background

Kidney lacks the regenerative capacity to replace nephrons lost during injury and disease resulting in end-stage kidney disease (ESKD). Due to their therapeutic properties, stem cells have become a promising candidate for the creation of new disease treatments including kidney injury. Urine-derived stem cells (USCs) are multipotent stem cells that originate in the kidney with high expandability, self-renewal capacity.

Methods

USCs are isolated from human urine samples and plated on gelatin coated plates for culturing in vitro. We employed mouse models of glycerol-induced rhabdomyolysis (Rhabdo) or unilateral nephrectomy with clamping ischemia reperfusion injury (UNI/R) to induce AKI. The homing and incorporation of luciferase transfected USCs in the mice was measured using the InVivoPLOT™ (InVivo Analytics) and were reconstructed with InVivoAx™ software at various timepoints (3h, 24h and 48h). To evaluate the therapeutic effects of USCs on injured human kidney cell types, we cultured kidney organoids from human induced pluripotent stem cells (hiPSCs). We established a nephrotoxic injury model of AKI by adding cisplatin (5 μM) to kidney organoid and followed up with a treatment of 5 x 10⁴ USCs for 48h.

Results

InVivoAnalytics software confirmed the presence of luc-USCs in both Rhabdo and UNI/R models within 3h of injection and localizations persisted upto 48h. Immunostaining confirmed USC localization in renal tubules and glomeruli of injured mice. Improved morphology as well as reduced kidney injury molecule-1 (KIM-1) (p<0.05) were observed in treated group compared to untreated group. When treated with USCs, cisplatin-injured organoids showed reduced expression of KIM-1 as well as cytotoxicity (p < 0.001). USCs incorporated within injured organoids differentiated into tubule (LTL+) and glomeruli (NEPHRIN+) cells.

Conclusion

The current study explored the USC’s ability to home to sites of injury in multiple models of AKI including rhabdomyolysis, IR injury, and drug-induced nephrotoxicity. USCs demonstrated a differentiation potential for renal cell types within injured kidney organoids. Taken together, these results indicate that USCs can home to a site of injury and may reduce the damage done to tubule cells during AKI suggesting requirement of further development.

Funding

• Veterans Affairs Support