Dongxu Hua1,2, Zheng Ju1,2,3, Xiaojie Gan1,2,3, Qi Wang1,2,3, Chenghuan Luo1,2, Jian Gu1,2, Yue Yu1,2. 1. The First School of Clinical Medicine & Hepatobiliary Center of First Affiliated Hospital, Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing 210000, China. 2. Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, Nanjing 210000, China. 3. Translational Medicine Research Center of Affiliated Jiangning Hospital, Liver Transplantation Center of First Affiliated Hospital, and Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing 210000, China.
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.
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.
Authors: Hossein Nejadnik; James H Hui; Erica Pei Feng Choong; Bee-Choo Tai; Eng Hin Lee Journal: Am J Sports Med Date: 2010-04-14 Impact factor: 6.202
Authors: Kiichi Nakahira; Jeffrey Adam Haspel; Vijay A K Rathinam; Seon-Jin Lee; Tamas Dolinay; Hilaire C Lam; Joshua A Englert; Marlene Rabinovitch; Manuela Cernadas; Hong Pyo Kim; Katherine A Fitzgerald; Stefan W Ryter; Augustine M K Choi Journal: Nat Immunol Date: 2010-12-12 Impact factor: 25.606