Abstract OBJECTIVE: To evaluate the efficacy of intraperitoneal transplantation of microencapsulated HepG2 cells in rats with hepatolenticular degeneration (HLD). METHODS: HLD was induced by copper-overloaded diet with forage containing 1 g/kg copper sulfate and water with 0.185% copper sulfate for 12 weeks in rats. One hundred and twenty three-month-old male Wistar rats were randomly intraperitoneal injected with normal saline (NS), microencapsulated HepG2 cells or non-microencapsulated HepG2 cells 9 weeks after copper-overloaded diet. Blood or liver samples were obtained at five time points: 3, 7, 14, 21 and 28 days after transplantation (n=8). The other 8 rats receiving normal diet were used as the control group. Serum levels of ALT, AST, albumin and Cu and liver Cu contents were measured. RESULTS: Serum ALT, AST and Cu levels and liver Cu contents in the NS-treated HLD, microencapsulated HepG2 cells and non-microencapsulated HepG2 cells transplantation groups increased significantly at all time points, in contrast, serum albumin levels decreased significantly in the NS-treated HLD and non-microencapsulated HepG2 cells transplantation groups compared with those in the control group at all time points (P<0.05), but serum albumin levels in the microencapsulated HepG2 cells transplantation restored to the level of the control group 28 days after transplantation. Serum ALT, AST and Cu levels and liver Cu contents in the microencapsulated HepG2 cells and non-microencapsulated HepG2 cells transplantation groups were significantly lower, in contrast, albumin levels were higher than those in the NS-treated HLD group on almost time points (P<0.05). Serum levels of ALT, AST and Cu and liver Cu contents in the microencapsulated HepG2 cells transplantation group decreased 7 or 14 days after transplantation, while serum albumin levels increased significantly 14 days after transplantation compared with those in the non-microencapsulated HepG2 cells transplantation group (P<0.05). CONCLUSIONS: Intraperitoneal transplantation of microencapsulated HepG2 cells can relieve hepatic damage, reduce serum and liver Cu levels, and improve copper metabolism, therefore it is promising for the treatment of HLD.［Chin J Contemp Pediatr, 2010, 12 (12):959-962］
LIN Hai-Long,CHEN Jie,HUANG Le-Ting et al. Efficacy of microencapsulated HepG2 cells transplantation in rats with hepatolenticular degeneration[J]. 中国当代儿科杂志, 2010, 12(12): 959-962.
LIN Hai-Long,CHEN Jie,HUANG Le-Ting et al. Efficacy of microencapsulated HepG2 cells transplantation in rats with hepatolenticular degeneration[J]. CJCP, 2010, 12(12): 959-962.
［1］Schilsky ML. Wilson disease:current status and the future. Biochimie［J］, 2009, 91(10): 1278-1281.
［2］Mei J, Sgroi A, Mai G, Baertschiger R, Gonelle-Gispert C, Serre-Beinier V, et al. Improved survival of fulminant liver failure by transplantation of microencapsulated cryopreserved porcine hepatocytes in mice［J］. Cell Transplant, 2009, 18(1): 101-110.
［3］Kang IK, Moon JS, Jeon HM, Meng W, Kim YI, Hwang YJ, et al. Morphology and metabolism of Ba-alginate encapsulated hepatocytes with galactosylated poly(allyl amine) and poly(vinyl alcohol) as extracellular matrices［J］. J Mater Sci Mater Med, 2005,16(6): 533-539.
［4］Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR. Phosphorylation of c-jun mediated by MAP kinases［J］. Nature, 199l, 353(6345): 670-674.
［5］Malhi H, Irani AN, Volenherg I, Schilsky ML, Gupta S. Early cell transplantation in LEC rats modeling Wilson's disease eliminates hepatic copper with reversa of liver disease［J］. Gastroenterology, 2002, 122(2): 438-447.
［6］Orive G, Hernández RM, Rodríguez Gascón A, Calafiore R, Chang TM, de Vos P, et al. History, challenges and perspectives of cell microencapsulation［J］. Trends Biotechnol, 2004, 22(2): 87-92.
［7］Ahmad TA, Fujioka H, Eguchi S, Yanaga K, Kamohara Y, Furui J, et al. Long-term effect of hepatocyte transplantation on fulminant hepatic failure in rats［J］. Hepatogastroenterology, 2003, 50(50): 467-471.
［8］Carruba G. Aromatase in nontumoral and malignant human liver tissues and cells［J］. Ann N Y Acad Sci, 2009, 1155:187-193.
［9］Suzuki KT, Kanno S, Misawa S, Aoki Y. Copper metabolism leading to and following acute hepatitis in LEC rats［J］. Toxicology, 1995, 97(1-3): 81-92.
［10］Friendman LS, Yarze JC. Zinc in the Treatment of Wilson's disease: how it works［J］. Gastroenterology, 1993, 104(5): 1566-1568.
