Liver fibrosis is a leading cause of morbidity and mortality worldwide, and the prevalence of chronic liver disease is expected to increase in parallel with obesity and type 2 diabetes mellitus epidemics.1 As there is currently no Food and Drug Administration (FDA)-approved drug treatment for liver fibrosis, a liver transplant is the only curative treatment for a minority of individuals who develop cirrhosis-associated complications such as liver cancer and liver failure. In the face of an acute organ shortage, there is a growing impetus to better understand the precise cellular and molecular mechanisms of adult liver repair and regeneration, so that clinically relevant therapeutic targets can be identified. In adults, after an acute liver injury, ‘normal’ regeneration occurs through the proliferation and expansion of remaining healthy hepatocytes and cholangiocytes, and there is minimal involvement of liver progenitors. By contrast, repair during chronic liver injury involves the proliferation of progenitor cells and cells with certain stem-like properties to differentiate into both hepatocytes and cholangiocytes, and thus support the restoration of liver function.2 3 What are the identity and/or origin of these liver progenitors? Multiple progenitor markers have been proposed, but none are completely specific as recent studies demonstrate that liver progenitors are actually a heterogeneous population that contains a variety of cell types, ranging from more primitive progenitors to more differentiated cells (eg, hepatocyte-like). Indeed, in adult mice, progenitors include biliary-like cells (also known as ‘oval cells’ in rodents) which arise in the ductal region, as well as progenitors around the central vein, de-differentiated hepatocytes or cholangiocytes, as well as multipotent mesenchymal stem cells (MSC) which also exhibit immunomodulatory properties.3 4 Similar …

中文翻译：

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利用肝祖细胞治疗肝纤维化：朝着正确方向迈出的一步？

肝纤维化是全球发病率和死亡率的主要原因，预计慢性肝病的患病率将与肥胖和 2 型糖尿病流行同步增加。 1 由于目前没有食品和药物管理局 (FDA) 批准的药物对于肝纤维化的治疗，对于少数患有肝硬化相关并发症（如肝癌和肝功能衰竭）的人来说，肝移植是唯一的治疗方法。面对急性器官短缺，人们越来越需要更好地了解成人肝脏修复和再生的精确细胞和分子机制，从而确定临床相关的治疗靶点。在成人中，急性肝损伤后，“正常”再生是通过剩余的健康肝细胞和胆管细胞的增殖和扩张而发生的，并且肝祖细胞的参与很少。相比之下，慢性肝损伤期间的修复涉及祖细胞和具有某些干细胞样特性的细胞的增殖，以分化为肝细胞和胆管细胞，从而支持肝功能的恢复。 2 3这些肝祖细胞？已经提出了多种祖细胞标记，但没有一个是完全特异性的，因为最近的研究表明，肝祖细胞实际上是一个异质群体，包含多种细胞类型，从更原始的祖细胞到更分化的细胞（例如，肝细胞样细胞）。事实上，在成年老鼠身上，