Immortalized canine adipose-derived mesenchymal stem cells alleviate gentamicin-induced acute kidney injury by inhibiting endoplasmic reticulum stress in mice and dogs

Adipose-derived mesenchymal stem cells have been used to treat acute kidney injury (AKI). The role of endoplasmic reticulum (ER) stress in AKI treatment with canine adipose-derived mesenchymal stem cells (cADSCs) remains unknown. This study intended to investigate the therapeutic effects of cADSCs cultured in different media on AKI in mice and dogs and reveal the role of ER stress in this process. The mice were divided into two branches: a control group and a gentamicin induced group (this group treated with low-serum ADSC or highserum ADSC or 4-phenylbutyric acid (4-PBA)). The dogs were divided into control, model, and cell-injected groups. To suppress ER stress, mice were simultaneously treated with 4-PBA. The results showed there were improvements in renal function and tissue damage and a corresponding decrease in ER stress in the kidneys of the mice that received cell injection. However, the cells cultured with 2% FBS showed a better growth state and resulted in lower ER stress levels in treated kidneys. In the 4-PBA-treated group, ER stress was suppressed, and there was corresponding kidney injury recovery. Similarly, both kidney damage and ER stress were alleviated after AKI dogs were injected with the cells. Our findings reveal that both allogeneic and xenogeneic cADSCs were effective treatments for AKI by inhibiting ER stress. These results also provide evidence for a new clinical therapy for acute renal disease in pets.