The deposition of extracellular matrix and hyperplasia of connective tissue characterizes chronic liver disease called hepatic fibrosis. Progression of hepatic fibrosis may lead to hepatocellular carcinoma. At this stage, only liver transplantation is a viable option. However, the number of possible liver donors is less than the number of patients needing transplantation. Consequently, alternative cell therapies based on non-stem cells (e.g., fibroblasts, chondrocytes, keratinocytes, and hepatocytes) therapy may be able to postpone hepatic disease, but they are often ineffective. Thus, novel stem cell-based therapeutics might be potentially important cutting-edge approaches for treating liver diseases and reducing patient’ suffering. Several signaling pathways provide targets for stem cell interventions. These include pathways such as TGF-β, STAT3/BCL-2, NADPH oxidase, Raf/MEK/ERK, Notch, and Wnt/β-catenin. Moreover, mesenchymal stem cells (MSCs) stimulate interleukin (IL)-10, which inhibits T-cells and converts M1 macrophages into M2 macrophages, producing an anti-inflammatory environment. Furthermore, it inhibits the action of CD4⁺ and CD8⁺ T cells and reduces the activity of TNF-α and interferon cytokines by enhancing IL-4 synthesis. Consequently, the immunomodulatory and anti-inflammatory capabilities of MSCs make them an attractive therapeutic approach. Importantly, MSCs can inhibit the activation of hepatic stellate cells, causing their apoptosis and subsequent promotion of hepatocyte proliferation, thereby replacing dead hepatocytes and reducing liver fibrosis. This review discusses the multidimensional therapeutic role of stem cells as cell-based therapeutics in liver fibrosis.

细胞外基质沉积和结缔组织增生是慢性肝病（称为肝纤维化）的特征。肝纤维化的进展可能导致肝细胞癌。现阶段，只有肝移植是可行的选择。然而，可能的肝脏捐献者数量少于需要移植的患者数量。因此，基于非干细胞（例如，成纤维细胞、软骨细胞、角质形成细胞和肝细胞）疗法的替代细胞疗法可能能够推迟肝病的发生，但它们通常是无效的。因此，基于干细胞的新型疗法可能是治疗肝病和减少患者痛苦的潜在重要前沿方法。多种信号通路为干细胞干预提供了靶点。这些途径包括 TGF-β、STAT3/BCL-2、NADPH 氧化酶、Raf/MEK/ERK、Notch 和 Wnt/β-连环蛋白等途径。此外，间充质干细胞 (MSC) 会刺激白细胞介素 (IL)-10，后者会抑制 T 细胞并将 M1 巨噬细胞转化为 M2 巨噬细胞，从而产生抗炎环境。此外，它还抑制 CD4 ⁺和 CD8 ⁺ T 细胞的作用，并通过增强 IL-4 合成来降低 TNF-α 和干扰素细胞因子的活性。因此，间充质干细胞的免疫调节和抗炎能力使其成为一种有吸引力的治疗方法。重要的是，间充质干细胞可以抑制肝星状细胞的活化，导致其凋亡并随后促进肝细胞增殖，从而取代死亡的肝细胞，减少肝纤维化。 这篇综述讨论了干细胞作为基于细胞的疗法在肝纤维化中的多维治疗作用。