Adipose-derived stem cells reduce liver oxidative stress and autophagy induced by ischemia-reperfusion and hepatectomy injury in swine

Aims: Hepatic ischemia-reperfusion (I/R) injury is an unavoidable complication of liver surgery, often resulting in postoperative complications and liver dysfunction. Adipose-derived stem cells (ADSCs) have been recognized as a potential tool to be exploited in the field of regenerative medicine for the treatment of a variety of diseases. In the present study, the efficacy of ADSCs in a porcine I/R model of laparoscopic hepatectomy was evaluated. Main methods: Twelve Bama miniature pigs were randomly divided into IRI and ADSCs group. ADSCs were injected through the liver parenchyma following a partial laparoscopic hepatectomy. The roles of ADSCs on oxidative stress and autophagy were analyzed. Key findings: It was observed that serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-BIL) and lactate dehydrogenase (LDH) was significantly decreased in response to the ADSC treatment. The data were suggestive of the mechanism of action through which ADSCs exert their attenuating effects on oxidative stress by increasing the activity of superoxide dismutase (SOD), and by suppressing the generation of both myeloperoxidase (MPO) and malondialdehyde (MDA). Moreover, the expression of the critical markers of autophagy including Beclinl, ATG5, ATG12 and LC3II all decreased, whereas expression of P62 increased during phagophore expansion. Significance: In conclusion, ADSCs attenuate hepatic I/R and hepatectomy-induced liver damage by reducing oxidative stress and inhibiting autophagy.