Abstract: SA-PO0283
Extracellular Vesicles from Female Cells Enhance Proliferation and Recovery in AKI
Session Information
- AKI: Mechanisms - Cell Signaling
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Kelly, Katherine J., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Greene, Zoe, Brown University, Providence, Rhode Island, United States
- Campbell, Jillian R., Richard L Roudebush VA Medical Center, Indianapolis, Indiana, United States
- Gunderman, Luke D., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Dominguez, Jesus H., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background
Acute kidney injury (AKI) is frequent and deadly. New approaches to treatment are needed. In experimental ischemia/reperfusion, we have shown that extracellular vesicles (EV, exosomes), given after renal failure is established, improve kidney function and structure. Like most basic and clinical renal studies, that work was conducted in males. Thus many factors that result in protection (which could be applied to males), recovery or severe injury and failed repair may not be discoverable.
Methods
The effect of EV of female origin in a model of renal ischemia/reperfusion injury on renal function, structure, inflammation and proliferation was evaluated. EV, membrane bound nanovesicles released from many cells contain mRNA and other signaling molecules that serve in cell-cell communication. The cargo of released EV varies with the type and state of the originating cell.
Results
EV altered the biology of cells from kidneys of different sex and age. Cells from male and older individuals proliferate more slowly than those from female and younger kidneys. The addition of EV from female cells enhanced the proliferation of male tubular cells in culture. Conversely, male EV slowed proliferation of female cells. As in previous studies in experimental ischemia/reperfusion, serum creatinine and histological evidence of injury were improved within 24 hours of delivery of EV from renal tubular cells. In a more severe injury model, EV from female tubular cells were more effective than those from male cells. Protection was characterized by decreased infiltration of neutrophils and macrophages and increased tubular cell proliferation. Levels of anti-inflammatory interleukin-10 were higher in kidneys treated with male EV than in postischemic kidneys and even higher in kidneys after treatment with EV of female origin.
Conclusion
Extracellular vesicles from female renal cells have anti-inflammatory and pro-proliferation effect on postischemic kidneys and result in improved renal function and structure. Examining the differences between male and female EV and kidneys will provide therapeutic targets.
Acknowledgment
This work is supported by a VA Merit award.
| creatinine (mg/dl) | % damaged tubules | neutrophils/hpf | macrophages/hpf | proliferating cells/hpf | Interleukin 10 (pg/g) | |
| sham | 0.27±0.03 | 0.7±0.1 | 0.2±0.2 | 0±0 | 0.33±0.33 | 153±26 |
| ischemia/vehicle | 2.63±0.09 | 41.2±6 | 6.2±1.2 | 4.8±0.7 | 2.5±0.72 | 60±9.5 |
| ischemia/male EV | 1.73±0.12 | 30±2 | 4.6±0.87 | 3.8±0.54 | 2.7±0.67 | 284±30 |
| ischemia/female EV | 1.07±0.09* | 17.8±2* | 2±0.45* | 2.2±0.48* | 3.8±0.95 | 472±36* |
Values are 48 hours after surgery; 24 hours after EV; * p<0.04 vs male
Funding
- Veterans Affairs Support