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Kidney Week

Abstract: TH-PO049

PAC-Mediated AKI Protection Is Critically Mediated but Does Not Exclusively Depend on Cell-Derived Microvesicles

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Author

  • Patschan, Daniel, Medizinische Hochschule Brandenburg, Brandenburg, Germany
Background

Acute Kidney Injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as reliable option for improving AKI outcomes in experimental AKI. Own studies focused on so-called Proangiogenic Cells (PACs). Mechanisms that contribute to PAC-mediated AKI protection include production / secretion of extracellular vesicles (EV). In addition, the cells most likely act by paracrinic processes (secretome). The current study evaluated whether AKI may be preventable by the administration of either PAC-derived EV and / or the secretome alone.

Methods

AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI - 40 minutes). Syngeneic murine PACs were stimulated with either melatonine, Angiopoietin-1 or -2, or with Bone Morphogenetic Protein-5 (BMP-5) for one hour, respectively. The four mediators were chosen since previous own studies showed improved PAC-mediated AKI protection after cell preconditioning with these substances. PAC-derived EV and the vesicle-depleted supernatant were subsequently collected and i.v. injected post-ischemia. Mice were analyzed 48 hours later.

Results

IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels. The only measure that improved AKI was the injection of EV, collected from native PACs. The following conditions worsened post-ischemic renal function even further: EV+Ang-1, EV+BMP-5, EV+melatonin, and EV+secretome+Ang-1.

Conclusion

Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived EV. The secretome, either collected from native or preconditioned cells does not prevent mice from ischemia-induced dysfunction. However, since previous data showed improved AKI-protection by PACs after cell preconditioning with certain mediators (Ang-1 and -2, melatonine, BMP-5), other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection. We suggest, that the mere presence of intact cells in the post-ischemic tissue is necessary for improving functional and structural outcome parameters under certain conditions.