Qiu Liyuan, Wang Jian, Wen Xinyu, Wang Haibin, Wang Yan, Lin Qiuxia, Du Zhiyan, Duan Cuimi, Wang Chunren, Wang Changyong
Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing-PR China.
Int J Artif Organs. 2012 Jun;35(6):458-65. doi: 10.5301/ijao.5000092.
Microencapsulated hepatocytes might solve immunological rejection, broadening a new perspective for the treatment of fulminant hepatic failure (FHF). However, the transplantation of microcapsulated hepatocytes is limited by low cell viability. Nevertheless, the co-microencapsulation of hepatocytes and human umbilical vein endothelial cells (HUVECs) may make the treatment of FHF more promising.
We prepared the microcapsules using the high-voltage electrostatic droplet spray method, transplanted the empty microcapsules, isolated hepatocytes, microcapsulated hepatocytes, and co-microencapsulated hepatocytes and HUVEC intraperitoneally into rat models of FHF induced by D-aminogalactose (D-gal). After 1, 3, and 7 days, and 2, 3, and 4 weeks posttransplantation, we calculated the mortality and assessed alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) levels in the serum of the model; evaluated the integrality and recovery of microcapsules; and stained with hematoxylin and eosin (H&E) the recovered microcapsules as well as the liver of the FHF rats.
Hepatocyte-specific functions, including the levels of ALT, AST, and ALB in the serum of the co-microencapsulation group, were significantly better than those in the other groups (p<0.05) from 2 to 4 weeks after transplantation. Moreover, cotransplantation of the microencapsulated hepatocytes and HUVECs decreased the mortality rate of the FHF rats. The recovered microcapsules were intact, and recovery was up to 90%. H&E staining showed that the microencapsulated cells were still alive, and the liver tissues had started to recover after 4 weeks posttransplantation.
The microcapsules have good biocompatibility and immunoprotection to protect the hepatocytes from immunological rejection. Cotransplantation of the microencapsulated hepatocytes and HUVECs could decrease mortality rates and improve liver function in FHF.
微囊化肝细胞或许能解决免疫排斥问题，为暴发性肝衰竭（FHF）的治疗开辟新视角。然而，微囊化肝细胞移植受细胞活力低的限制。不过，肝细胞与人脐静脉内皮细胞（HUVECs）的共微囊化可能使FHF的治疗更具前景。
我们采用高压静电液滴喷雾法制备微囊，将空微囊、分离的肝细胞、微囊化肝细胞以及肝细胞与HUVECs的共微囊化产物腹腔注射到由D-氨基半乳糖（D-gal）诱导的FHF大鼠模型中。在移植后1、3和7天以及2、3和4周，我们计算死亡率，并评估模型血清中的丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和白蛋白（ALB）水平；评估微囊的完整性和回收率；并用苏木精和伊红（H&E）对回收的微囊以及FHF大鼠的肝脏进行染色。
从移植后2至4周，共微囊化组血清中ALT、AST和ALB水平等肝细胞特异性功能显著优于其他组（p<0.05）。此外，微囊化肝细胞与HUVECs的共移植降低了FHF大鼠的死亡率。回收的微囊完整，回收率高达90%。H&E染色显示微囊化细胞仍存活，移植后4周肝脏组织已开始恢复。
微囊具有良好的生物相容性和免疫保护作用，可保护肝细胞免受免疫排斥。微囊化肝细胞与HUVECs的共移植可降低FHF的死亡率并改善肝功能。
