Rapid recovery of male cats with postrenal acute kidney injury by treating with allogeneic adipose mesenchymal stem cell-derived extracellular vesicles

Acute kidney injury (AKI) is a complex disease and can be generally divided into prerenal, intrarenal, and postrenal AKI (PR-AKI). Previous studies have shown that mesenchymal stem cells (MSCs)-derived extracellular vesicles 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 cell-derived extracellular vesicles (ADMSCEVs) on cat models of PR-AKI.

We demonstrate the efficacy of ADMSCEVs in the treatment of PR-AKI on cats. Our study also suggests six metabolites to be novel PR-AKI markers and to be potential targets for ADMSCEVs therapy. Our findings will be useful to improve clinical treatment of both animal and human PR-AKI patients with ADMSCEVs in the future.

The cat models of PR-AKI were established by using artificial urinary occlusion and then treated with ADMSCEVs. 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 ADMSCEVs.

Physiological and biochemical test showed that the ADMSCEVs could recover creatinine, urea nitrogen and plasma phosphorus to homeostasis efficiently. Blood routine analysis showed that leukocytes in PR-AKI cats with ADMSCEVs treatment returned to normal physiological range more quickly than that of control. UHPLC-MS/MS analysis revealed that the plasma metabolome profile of PR-AKI cats treated with ADMSCEVs 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. Conclusions: We demonstrate the efficacy of ADMSCEVs in the treatment of PR-AKI on cats. Our study also suggests six metabolites to be novel PR-AKI markers and to be potential targets for ADMSCEVs therapy. Our findings will be useful to improve clinical treatment of both animal and human PR-AKI patients with ADMSCEVs in the future.