Human amniotic mesenchymal stromal cells alleviate acute liver injury by inhibiting the pro-inflammatory response of liver resident macrophage through autophagy.

BACKGROUND

The activation and polarization of macrophages are crucial during the pathogenesis of liver injury induced by the toxin. Human amniotic mesenchymal stromal cells (hAMSCs) are newly identified mesenchymal stem cells and have been shown to have an immunoregulatory ability for multiple autoimmune diseases.

METHODS

Mice were intraperitoneally injected with Acetaminophen (APAP) to establish a liver injury model. hAMSCs were injected through the tail vein, and the liver function was observed through a liver function and pathology analysis. To test the regulative ability of hAMSCs , the supernatant of hAMSCs were collected and co-cultured with Kupffer cells (KCs). Liposome was used to abolish the function of KCs .

RESULTS

Infusion of hAMSCs reduced the level of liver function injury and inflammation expression in APAP-induced liver injury. hAMSCs markedly promoted M2 polarization of KCs instead of M1 polarization . Furthermore, the mechanism study also proved that hAMSCs reduced autophagy, as revealed by down-regulated LC3B-II levels. The elimination of KCs abolished the protective ability of hAMSCs in liver injury, which resulted in a significant increase of liver pathogenesis along with an increase in alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) levels.

CONCLUSIONS

Our results proved that hAMSCs suppressed M1 polarization and promoted M2 polarization of KCs through regulating autophagy in the model of APAP-treated livers. Thus, the injury of the liver was attenuated. This study provides us a new therapeutic strategy for the disease of acute liver injury.