Rapid Recovery of Male Cats with Postrenal Acute Kidney Injury by Treating with Allogeneic Adipose Mesenchymal Stem Cell-derived Exosomes

Abstract:

Background: Acute kidney injury (AKI) is a complex disease and can be generally divided into prerenal, in-trarenal, and postrenal AKI (PR-AKI). Previous studies have shown that mesenchymal stem cells (MSCs)-derived exosomes have protective function on prerenal and intrarenal AKI treatment, but whether they have therapeutic efficacy on PR-AKI remains unclear. In this study, we investigated the therapeutic efficacy of allogeneic adipose mesenchymal stem cells-derived exosomes (ADMSCEs) on a cat model of PR-AKI.

Methods: The cat models of PR-AKI were established by using artificial urinary occlusion and then treated with ADMSCEs. Histopathological section analysis, blood routine analysis, plasma biochemical test, imaging analysis, and plasma ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) were performed to evaluate the therapeutic efficacy of ADMSCEs.

Results: Physiological and biochemical test showed that the ADMSCEs could recover creatinine, urea nitrogen and plasma phosphorus to homeostasis efficiently. Blood routine analysis showed that leukocytes in PR-AKI cats with ADMSCEs treatment returned to normal physio-logical range more quickly than that of control. UHPLC-MS/MS analysis revealed that the plasma metabolome profile of PR-AKI cats treated with ADMSCEs was highly similar to that of normal cats. Furthermore, UHPLC-MS/MS analysis also revealed six metabolites (carnitine, melibiose, D−glucosamine, cytidine, dihydroorotic acid, stachyose) in plasma were highly correlated with the dynamic process of PR-AKI on cats and were potential novel targets for ADMSCEs therapy.

Conclusions: Our findings demonstrate the efficacy of ADMSCEs in the treatment of PR-AKI on cats, and provide valuable reference for translational medicine research on PR-AKI treatment in elderly patients with MSCs-derived exosomes in the future.