Transplantation of Hepatocyte Spheroids Covered with Mesenchymal Stem Cells

背景：肝细胞的长期培养具有重要的治疗应用价值，尤其是细胞移植或生物人工肝。为了优化肝细胞功能，我们假设在与间充质干细胞(MSCs)共培养的肝细胞球体中，肝细胞功能可以维持在高水平的蛋白质合成。方法：在摇床悬浮培养中形成并维持小鼠肝细胞球体，加入或不加入MSC共培养。对小鼠肝细胞球体的存活率、球体形成动力学、肝功能和生化活性进行了检测，直至培养7天。结果：我们观察到，与对照条件相比，MSCs促进了尿素的生成并稳定了肝细胞球体的完整性，最长可达7天。结论：肝细胞可形成球体，并可在7d内维持较高的蛋白质合成水平。肝细胞与间充质干细胞在球形微环境中的共培养进一步稳定了肝脏功能和球形完整性。

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.