Department of Hepatobiliary Surgery, The Affiliated DrumTower Hospital of Nanjing University Medical School, Nanjing, China.
Transplantation. 2009 Nov 27;88(10):1178-85. doi: 10.1097/TP.0b013e3181bc288b.
Hepatocyte transplantation is an alternative to liver transplantation, which is hampered by short survival time and immunorejection. In this study, we investigated the specific functions of hepatocytes coencapsulated with bone marrow mesenchymal stem cells (MSCs) in vitro, and we further examined whether transplantation of coencapsulated hepatocytes and MSCs could enhance the ability of hepatocytes to alleviate acute liver failure in vivo.
Rat hepatocytes and MSCs were isolated and coencapsulated by alginate-poly-l-lysine-alginate microencapsulation. Cell functions were monitored during the course of cell culturing. Acute liver failure in rats was induced by d-galactosamine administration. These rats were subjected to intraperitoneal transplantation of coencapsulated hepatocytes with MSCs, encapsulated hepatocytes alone, or empty vehicles after 24 hr. The survival rate and liver functions were assessed. Immunofluorescence microscopy was used for the analysis of coencapsulated cells before and 7 days after transplantation.
Hepatocyte-specific functions, including albumin secretion and urea synthesis, were all significantly improved in the coencapsulation group compared with the encapsulated hepatocytes group (P<0.05). Similar trend was observed for cell cycle analysis of hepatocytes. Intraperitoneal transplantation of coencapsulated hepatocytes with MSCs not only increased the survival rate but also improved liver functions in a rat model of acute liver failure. Some MSCs transdifferentiated into hepatocyte-like cells in vivo, which expressed albumin, a typical marker of hepatocyte.
Encapsulation of hepatocytes and MSCs improved hepatocyte-specific functions in vitro and in vivo. Transplantation of coencapsulated hepatocytes and MSC might be a promising strategy for cell-based therapy for acute liver diseases.
肝细胞移植是肝移植的一种替代方法，但由于生存时间短和免疫排斥，受到限制。在这项研究中，我们研究了与骨髓间充质干细胞（MSCs）共包封的肝细胞的特定功能，并且进一步研究了共包封的肝细胞和 MSCs 的移植是否可以增强肝细胞缓解体内急性肝衰竭的能力。
从大鼠中分离肝细胞和 MSCs 并通过藻酸盐-聚赖氨酸-藻酸盐微囊化共包封。在细胞培养过程中监测细胞功能。通过 D-半乳糖胺给药诱导大鼠急性肝衰竭。在 24 小时后，这些大鼠接受了共包封的肝细胞与 MSCs、单独包封的肝细胞或空载体的腹腔内移植。评估了存活率和肝功能。免疫荧光显微镜用于分析移植前和移植后 7 天的共包封细胞。
与单独包封的肝细胞组相比，共包封组的肝细胞特异性功能，包括白蛋白分泌和尿素合成，均有显著改善（P<0.05）。肝细胞细胞周期分析也观察到了类似的趋势。腹腔内共移植肝细胞和 MSCs 不仅提高了存活率，而且改善了急性肝衰竭大鼠的肝功能。一些 MSCs 在体内转分化为肝细胞样细胞，表达白蛋白，这是肝细胞的典型标志物。
肝细胞和 MSCs 的包封在体外和体内均改善了肝细胞的特异性功能。共包封的肝细胞和 MSC 的移植可能是急性肝疾病细胞治疗的一种有前途的策略。
