Macrophages, a new hope for the treatment of liver fibrosis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SHU Yuke ¹ , PENG Wei ² ,  SHI Yujun ¹ , WEN Tianfu ²

1. Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, P.R. China;
2. Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

SHI Yujun, Email: shiyujun@scu.edu.cn

Keywords：

liver fibrosis; macrophages; liver resection surgery

DOI：

10.7507/1007-9424.202211004

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Evidence from numerous animal models and clinical studies in recent years has demonstrated that macrophages play an important role in the regulation of liver fibrosis regression. The safety and efficacy of utilizing autologous macrophages for the treatment of liver fibrosis have been demonstrated in patients and shows promising application prospects, but the therapeutic effects need to be improved. Cirrhotic liver undergoes a process of marked extracellular matrix degradation after partial hepatectomy surgery, and single-cell sequencing identified multiple restorative macrophage subsets that express different matrix metalloproteinases (MMPs) at high levels. Future efforts to further characterize this population of macrophages and improve their enrichment in the liver may allow macrophage therapy to be a highly effective strategy to reverse liver fibrosis.

Citation： SHU Yuke, PENG Wei, SHI Yujun, WEN Tianfu. Macrophages, a new hope for the treatment of liver fibrosis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(12): 1559-1561. doi: 10.7507/1007-9424.202211004 Copy

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10.	Cheng D, Chai J, Wang H, et al. Hepatic macrophages: Key players in the development and progression of liver fibrosis. Liver Int, 2021, 41(10): 2279-2294.
11.	Ramachandran P, Pellicoro A, Vernon MA, et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc Natl Acad Sci U S A, 2012, 109(46): E3186-E3195. doi: 10.1073/pnas. 1119964109.
12.	Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol, 2014, 60(5): 1090-1096.
13.	Moroni F, Dwyer BJ, Graham C, et al. Safety profile of autologous macrophage therapy for liver cirrhosis. Nat Med, 2019, 25(10): 1560-1565.
14.	King A, Barton D, Beard HA, et al. Repeated autologous infusions of stem cells in cirrhosis (REALISTIC): a multicentre, phase Ⅱ, open-label, randomised controlled trial of repeated autologous infusions of granulocyte colony-stimulating factor (GCSF) mobilised CD133⁺ bone marrow stem cells in patients with cirrhosis. A study protocol for a randomised controlled trial. BMJ Open, 2015, 5(3): e007700. doi: 10.1136/bmjopen-2015-007700.

1. Asrani SK, Devarbhavi H, Eaton J, et al. Burden of liver diseases in the world. J Hepatol, 2019, 70(1): 151-171.
2. Palmer WC, Patel T. Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma. J Hepatol, 2012, 57(1): 69-76.
3. Caligiuri A, Gentilini A, Pastore M, et al. Cellular and molecular mechanisms underlying liver fibrosis regression. Cells, 2021, 10(10): 2759. doi: 10.3390/cells10102759.
4. Matteson EL, Kelly C, Distler JHW, et al. Nintedanib in patients with autoimmune disease-related progressive fibrosing interstitial lung diseases: subgroup analysis of the INBUILD trial. Arthritis Rheumatol, 2022, 74(6): 1039-1047.
5. Klepfish M, Gross T, Vugman M, et al. LOXL2 inhibition paves the way for macrophage-mediated collagen degradation in liver fibrosis. Front Immunol, 2020, 11: 480. doi: 10.3389/fimmu.2020.00480.
6. Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol, 2021, 18(3): 151-166.
7. Watanabe Y, Tsuchiya A, Terai S. The development of mesenchymal stem cell therapy in the present, and the perspective of cell-free therapy in the future. Clin Mol Hepatol, 2021, 27(1): 70-80.
8. Shi M, Li YY, Xu RN, et al, Mesenchymal stem cell therapy in decompensated liver cirrhosis: a long-term follow-up analysis of the randomized controlled clinical trial. Hepatol Int, 2021, 15(6): 1431-1441.
9. Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol, 2017, 66(6): 1300-1312.
10. Cheng D, Chai J, Wang H, et al. Hepatic macrophages: Key players in the development and progression of liver fibrosis. Liver Int, 2021, 41(10): 2279-2294.
11. Ramachandran P, Pellicoro A, Vernon MA, et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc Natl Acad Sci U S A, 2012, 109(46): E3186-E3195. doi: 10.1073/pnas. 1119964109.
12. Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol, 2014, 60(5): 1090-1096.
13. Moroni F, Dwyer BJ, Graham C, et al. Safety profile of autologous macrophage therapy for liver cirrhosis. Nat Med, 2019, 25(10): 1560-1565.
14. King A, Barton D, Beard HA, et al. Repeated autologous infusions of stem cells in cirrhosis (REALISTIC): a multicentre, phase Ⅱ, open-label, randomised controlled trial of repeated autologous infusions of granulocyte colony-stimulating factor (GCSF) mobilised CD133⁺ bone marrow stem cells in patients with cirrhosis. A study protocol for a randomised controlled trial. BMJ Open, 2015, 5(3): e007700. doi: 10.1136/bmjopen-2015-007700.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Macrophages, a new hope for the treatment of liver fibrosis

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