巨噬细胞,肝纤维化治疗的新希望

Macrophages,a new hope for the treatment of liver fibrosis

近年来许多来自动物模型和临床的证据表明,巨噬细胞在肝纤维化调节中发挥重要作用。利用自体巨噬细胞治疗肝纤维化的安全性和有效性已在临床得到证明并显示了良好的应用前景,但其治疗效果仍然有待提高。硬化肝脏在部分肝脏切除手术后经历了一个细胞外基质显著降解的过程,单细胞测序鉴定出了多个高水平表达不同基质金属蛋白酶(matrix metalloproteinases,MMPs)的促修复性巨噬细胞亚群。未来若能进一步分离鉴定这群巨噬细胞并提高其在肝脏的富集,可使巨噬细胞治疗成为一种高效逆转肝纤维化的策略。

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.