Abstract: TH-PO328

Human Renal Tubular Cells and Their Exosomes in Rat Ischemic Renal Injury

Session Information

Category: Acute Kidney Injury

  • 002 AKI: Repair and Regeneration

Authors

  • Dominguez, Jesus H., VAMC, Indianapolis, Indiana, United States
  • Kelly, Katherine J., Indiana University, Indianapolis, Indiana, United States
  • Dominguez, James M., Indiana University, Indianapolis, Indiana, United States
Background

We previously showed that intravenous infusion of 3E10 rat renal cells, previoulsy subjected to ischemia preconditioning, prevented rat acute kidney injury (AKI) one day after severe ischemia. The donor cells were found anchored to recipient kidney tubules in relatively small numbers.

Methods

We hypothesized that the relatively small number of donated cells amplified their action by releasing their exosomes in situ. Thus, a local spread of exosomes derived from ischemia preconditioned cells potentially amplified the effect. Therefore, normal human kidneys declined for transplantation were digested and their tubules stored frozen and then cultured, representing 70 % proximal tubular cells. These human cells or their exosomes were given intravenously to nude rats, and comparisons were made.

Results

We compared the protective effects of normal human kidney cells (HuCell) or their exosomes (HuExo) (from declined human kidneys) given intravenously, against untreated ischemia (Isch) 1 and 2 days after 50 minutes of bilateral renal ischemia in nude rats. A sham group was also included (Sh). We estimated each rat nephron received a maximum of 47 renal cells or 2E06 exosomes per injection. We found that 1 day after ischemia serum creatinine increased from 0.23 ± 0.02 , n = 4-5, mean ± SE, to 1.23 ± 0.07 in all ischemic groups. After 2 days, Isch continue to rise 2.26 ± 0.36, but Huexo, 0.41 ± 0.05 was similar to Sh, 0.36 ± 0.02, and lower than HuCell ± 0.85 ± 0.17, p <0.02. After 6 days, % damaged tubules in Isch 89 ± 2 was higher than HuCell 49 ± 4 ; HuExo 23 ± 2 and Sh 1.5 ± 0.2 ; p < 0.001. Fibrosis (% area) was also higher in Isch 26 ± 1.5 than HuCell 12 ± 0.7 , HuExo 8.5 ± 0.5 and Sh 5.5 ± 0.9 , p < 0.001.

Conclusion

We conclude that HuExo are superior agents than HuCell, although the latter were also effective. However, the probability for larger numbers of HuExo to reach all affected nephrons is likely higher. Also, HuExo were effective 1 day after severe ischemia, which greatly enhances their therapeutic advantage over all other therapies in AKI. Finally HuExo therapy of AKI is a very feasible therapy in the clinical setting.

Funding

  • NIDDK Support