Epithelial cells in the liver (known as hepatocytes) are high-performance engines of myriad metabolic functions and versatile responders to liver injury. As hepatocytes metabolize amino acids, alcohol, drugs, and other substrates, they produce and are exposed to a milieu of toxins and harmful byproducts that can damage themselves. In the healthy liver, hepatocytes generally divide slowly. However, after liver injury, hepatocytes can ramp up proliferation to regenerate the liver. Yet, on extensive injury, regeneration falters, and liver failure ensues. It is therefore critical to understand the mechanisms underlying liver regeneration and, in particular, which liver cells are mobilized during liver maintenance and repair. Controversies continue to surround the very existence of hepatic stem cells and, if they exist, their spatial location, multipotency, degree of contribution to regeneration, ploidy, and susceptibility to tumorigenesis. This review discusses these controversies. Finally, we highlight how insights into hepatocyte regeneration and biology in vivo can inform in vitro studies to propagate primary hepatocytes with liver regeneration-associated signals and to generate hepatocytes de novo from pluripotent stem cells.

肝脏中的上皮细胞（称为肝细胞）是无数代谢功能的高性能引擎，也是肝损伤的多功能反应器。当肝细胞代谢氨基酸、酒精、药物和其他底物时，它们会产生并暴露于毒素和有害副产物的环境中，这些副产物会损害自身。在健康的肝脏中，肝细胞通常分裂缓慢。然而，肝损伤后，肝细胞可以加速增殖以再生肝脏。然而，在大面积损伤时，再生能力减弱，肝功能衰竭随之而来。因此，了解肝脏再生的潜在机制至关重要，尤其是在肝脏维护和修复过程中动员了哪些肝细胞。围绕肝干细胞的存在以及如果它们存在的话，它们的空间位置仍存在争议，多能性、对再生的贡献程度、倍性和对肿瘤发生的易感性。本评论讨论了这些争议。最后，我们强调了对体内肝细胞再生和生物学的深入了解如何为体外研究提供信息，以传播具有肝再生相关信号的原代肝细胞，并从多能干细胞从头生成肝细胞。