INSERM U1149, Center for Research on Inflammation, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Am J Pathol. 2018 Jun;188(6):1316-1327. doi: 10.1016/j.ajpath.2018.03.008. Epub 2018 Apr 16.
Liver regeneration is a complex and unique process. When two-thirds of a mouse liver is removed, the remaining liver recovers its initial weight in approximately 10 days. The understanding of the mechanisms responsible for liver regeneration may help patients needing large liver resections or transplantation and may be applied to the field of regenerative medicine. All differentiated hepatocytes are capable of self-renewal, but different subpopulations of hepatocytes seem to have distinct proliferative abilities. In the setting of chronic liver diseases, a ductular reaction ensues in which liver progenitor cells (LPCs) proliferate in the periportal region. Although these LPCs have the capacity to differentiate into hepatocytes and biliary cells in vitro, their ability to participate in liver regeneration is far from clear. Their expansion has even been associated with increased fibrosis and poorer prognosis in chronic liver diseases. Controversies also remain on their origin: lineage studies in experimental mouse models of chronic injury have recently suggested that these LPCs originate from hepatocyte dedifferentiation, whereas in other situations, they seem to come from cholangiocytes. This review summarizes data published in the past 5 years in the liver regeneration field, discusses the mechanisms leading to regeneration disruption in chronic liver disorders, and addresses the potential use of novel approaches for regenerative medicine.
肝脏再生是一个复杂而独特的过程。当老鼠肝脏的三分之二被切除后，剩余的肝脏大约在 10 天内恢复到初始重量。了解负责肝脏再生的机制可能有助于需要进行大的肝切除术或肝移植的患者，也可能应用于再生医学领域。所有分化的肝细胞都具有自我更新的能力，但不同的肝细胞亚群似乎具有不同的增殖能力。在慢性肝病的情况下，会发生胆管反应，其中肝祖细胞 (LPC) 在门脉周围区域增殖。尽管这些 LPC 在体外具有分化为肝细胞和胆管细胞的能力，但它们参与肝脏再生的能力还远不清楚。它们的扩增甚至与慢性肝病中纤维化增加和预后较差有关。它们的起源也存在争议：最近在慢性损伤的实验性小鼠模型中的谱系研究表明，这些 LPC 来源于肝细胞去分化，而在其他情况下，它们似乎来自胆管细胞。本文综述了过去 5 年在肝脏再生领域发表的研究数据，讨论了导致慢性肝病中再生障碍的机制，并探讨了用于再生医学的新方法的潜在用途。
