Transplantation of Hepatocyte Spheroids Covered with Mesenchymal Stem Cells

背景：肝细胞的长期培养对肝细胞移植或生物人工肝的治疗应用具有重要价值。为了优化肝细胞功能，我们假设，肝细胞功能可以保持在一个高水平的蛋白质合成的肝细胞球体与间充质干细胞（MSC）共培养。方法：在有或无MSC共培养的情况下，在悬浮培养中形成小鼠肝细胞球状体并维持。球体的活力，球体形成的动力学，肝功能，和生化活性的小鼠肝细胞球体进行了测试，长达7天的文化。结果如下：我们观察到，与对照条件相比，MSC增强了尿素生成并稳定了肝细胞球体的完整性长达7天。结论：肝细胞形成球状体，并保持高水平的蛋白质合成长达7天。通过在球状体微环境中将肝细胞与MSC共培养，进一步稳定肝功能和球状体完整性。

Background : Long-term culture of hepatocyte is valuable for therapeutic applications, especially cell transplantation or the bioartificial liver. To optimize hepatocyte function, we hypothesized that hepatocyte function can be maintained at a high level of protein synthesis in hepatocyte spheroids co-cultured with mesenchymal stem cells(MSCs). Methods : Mouse hepatocyte spheroids were formed and maintained in a rocked suspension culture with or without MSC co-culture. Spheroid viability, kinetics of spheroid formation, hepatic functions, and biochemical activities of mouse hepatocyte spheroids were tested up to seven days of culture. Results : We observed that MSCs enhanced urea genesis and stabilized integrity of hepatocyte spheroids compared to control conditions up to seven days days. Conclusion : Hepatocytes formed spheroids and maintained a high level of protein synthesis up to seven days. Hepatic functionality and spheroid integrity were further stabilized by co-culture of hepatocytes with MSC's in the spheroid microenvironment.