共微囊化肝细胞和人脐静脉内皮细胞移植治疗暴发性肝衰竭

Transplantation of co-microencapsulated hepatocytes and HUVECs for treatment of fulminant hepatic failure.

作者信息

Qiu Liyuan, Wang Jian, Wen Xinyu, Wang Haibin, Wang Yan, Lin Qiuxia, Du Zhiyan, Duan Cuimi, Wang Chunren, Wang Changyong

机构信息

Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing-PR China.

出版信息

Int J Artif Organs. 2012 Jun;35(6):458-65. doi: 10.5301/ijao.5000092.

DOI:10.5301/ijao.5000092

PMID:22562371

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

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。

方法

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。