Vonada Anne, Grompe Markus
Department of Pediatrics, Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, Oregon, USA.
Hepatology. 2024 Oct 29. doi: 10.1097/HEP.0000000000001143.
The liver is a highly regenerative organ capable of significant proliferation and remodeling during homeostasis and injury responses. Experiments of nature in rare genetic diseases have illustrated that healthy hepatocytes may have a selective advantage, outcompete diseased cells, and result in extensive liver replacement. This observation has given rise to the concept of therapeutic liver repopulation by providing an engineered selective advantage to a subpopulation of beneficial hepatocytes. In vivo selection can greatly enhance the efficiency of both gene and cell transplantation therapies for hepatic diseases. In vivo hepatocyte selection has also enabled the expansion of human hepatocytes in animals, creating novel models of human liver disease and biology. Finally, recent work has shown that somatic mutations produce clonal expansion of injury-resistant hepatocytes in most chronic liver diseases. In this review, we will address the role of hepatocyte selection in disease pathophysiology and therapeutic strategies.
肝脏是一个具有高度再生能力的器官，在稳态和损伤反应过程中能够进行显著的增殖和重塑。对罕见遗传疾病的自然实验表明，健康的肝细胞可能具有选择性优势，胜过患病细胞，并导致肝脏大量替换。这一观察结果引发了通过为有益肝细胞亚群提供工程化的选择性优势来实现治疗性肝脏再填充的概念。体内选择可以大大提高肝脏疾病的基因治疗和细胞移植治疗的效率。体内肝细胞选择还能够在动物体内扩增人肝细胞，创建人类肝脏疾病和生物学的新型模型。最后，最近的研究表明，在大多数慢性肝病中，体细胞突变会导致抗损伤肝细胞的克隆性扩增。在这篇综述中，我们将探讨肝细胞选择在疾病病理生理学和治疗策略中的作用。
