A New Molecular Mechanism to Bioengineering a Liver

肝细胞移植具有许多潜在的应用前景。广布的动物 实验表明，肝细胞移植到肝脏或异位部位 生存、发挥作用，并积极参与再生过程。然而，我们的 对肝细胞植入及其显著增殖和分化的认识 再生潜力是有限的，即使初次肝细胞移植处于 在治疗遗传性和获得性人类疾病方面的应用家门口。我们 先前曾偶然观察到，正常肝细胞移植到 致死性肝病动物的腹膜腔向淋巴系统迁移 并设计了异位类肝脏有机化合物，将动物模型从致命的 代谢紊乱。肝细胞如何进入淋巴管以及是什么分子 产生异位质量的机制尚不清楚。我们 假设肝细胞必须借用一些分子机制 淋巴细胞用来迁移到淋巴管中。我们的兴趣将是研究异位细胞 移植和我们的应用程序的中心目标是将高度 有趣的观察，异位肝脏的产生，以潜在的临床应用 适用于肝病患者。

Hepatocyte transplantation has many potential applications. Extensive animal experiments have shown that hepatocytes transplanted in the liver or at ectopic sites survive, function, and actively participate in the regenerative process. However our understanding of hepatocyte engraftment and their remarkable proliferative and regenerative potential is limited, even if primary hepatocyte transplantation is at the doorstep of applications in the treatment of inherited and acquired human diseases. We previously made a serendipitous observation that normal hepatocytes transplanted in the peritoneal cavity of an animal with lethal liver disease migrate into the lymphatic system and engineer ectopic liver-like organoids that rescue an animal model from a fatal metabolic disorder. How hepatocytes enter the lymphatics and what molecular mechanism is responsible for the generation of ectopic mass is not known. We hypothesized that hepatocytes must borrow some of the molecular mechanism lymphocytes use to migrate into the lymphatics. Our interest will be to study ectopic cell transplantation and our central objective of our application is to translate a highly interesting observation, the generation of ectopic liver, to a potential clinical application for patients with liver diseases.