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

Abstract

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 in vitro, the supernatant of hAMSCs were collected and co-cultured with Kupffer cells (KCs). Liposome was used to abolish the function of KCs in vivo. 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 in vitro. Furthermore, the mechanism study also proved that hAMSCs reduced autophagy, as revealed by down-regulated LC3B-II levels. The elimination of KCs in vivo 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.

Human umbilical cord mesenchymal stem cells ameliorate acute liver failure by inhibiting apoptosis, inflammation and pyroptosis

“…Transplantation of MSCs improved liver function and prolonged the survival time of swine with ALF (20). Human amniotic MSCs improved acetaminophen-induced acute liver injury (21). Furthermore, exogenous MSCs were proved to survive in a mice body and homed to the injured liver to exert hepatoprotective function (22).…”

“…Available at https://dx.doi. org/10.21037/atm- 21 Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.…”

Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells

“…Acute liver injury (ALI) refers to abnormal liver function caused by various reasons. Studies showed that pretreatment with hAMSCs partially protected the acetaminophen-induced ALI by inhibiting Kupffer cells (KCs)-related innate immune inflammation and KCs autophagy [ 141 ] and that hAESCs and hAESC-CM significantly reduced hepatic inflammation and fibrosis in a high fat diet-induced non-alcoholic fatty liver disease model by inhibiting pSMAD 2/3 signaling and reducing the numbers of activated hepatic stellate cells and liver macrophages [ 142 ]. Furthermore, hepatocyte transplantation to treat liver disease is largely limited by the availability of the hepatocyte-like cells (HLCs).…”

Autophagy in liver diseases

“…These results suggest that Kupffer cell autophagy has an opposite effect on APAP hepatotoxicity compared to hepatocytes. This last observation may be useful for future therapeutic exploitation[ 630 ].…”