Abstract：
Liver disease is a major global health challenge. There is a shortage of liver donors worldwide, and hepatocyte transplantation (HT) may be an effective treatment to overcome this problem. However, the present approaches for generation of hepatocytes are associated with challenges, and interspecies chimera-derived hepatocytes produced by interspecies blastocyst complementation (IBC) may be promising donor hepatocytes because of their more comprehensive hepatic functions. In this study, we isolated mouse hepatocytes from mouse-rat chimeric livers using IBC and found that interspecies chimera-derived hepatocytes exhibited mature hepatic functions in terms of lipid accumulation, glycogen storage, and urea synthesis. Meanwhile, they were more similar to endogenous hepatocytes than hepatocytes derived in vitro. Interspecies chimera-derived hepatocytes could relieve chronic liver fibrosis and reside in the injured liver after transplantation. Our results suggest that interspecies chimera-derived hepatocytes are a potentially reliable source of hepatocytes and can be applied as a therapeutic approach for HT.
摘要：
肝病是一个重大的全球卫生挑战。全世界肝脏供体短缺,肝细胞移植（HT）可能是克服这一问题的有效治疗方法。然而,目前产生肝细胞的方法与挑战有关，种间囊胚互补（IBC）产生的种间嵌合体衍生的肝细胞可能是有前途的供体肝细胞，因为它们具有更全面的肝功能。在这项研究中,我们使用IBC从小鼠-大鼠嵌合肝脏中分离出小鼠肝细胞，并发现种间嵌合体衍生的肝细胞在脂质积累方面表现出成熟的肝功能，糖原储存，和尿素合成。同时,它们更类似于内源性肝细胞，而不是体外来源的肝细胞。种间嵌合体来源的肝细胞可以缓解慢性肝纤维化，并在移植后驻留在受损的肝脏中。我们的结果表明，种间嵌合体衍生的肝细胞是肝细胞的潜在可靠来源，可用作HT的治疗方法。
