LONG-TERM ENGRAFTMENT OF HEPATOCYTES TRANSPLANTED ON BIODEGRADABLE POLYMER SPONGES

Hepatocyte transplantation may provide an alternative to orthotopic li ver transplantation to treat liver failure. However, suitable systems to transplant hepatocytes and promote long-term engraftment must be de veloped. In this study, highly porous, biodegradable sponges were fabr icated from poly (L-lactic acid) (PLA), and poly (DL-lactic-co-glycoli c acid) (PLGA), and utilized to transplant hepatocytes into the mesent ery of three groups of Lewis rats. The portal vein was shunted to the inferior vena cava in one group of rats (PCS). The second group of ani mals received a PCS and a 70% hepatectomy on the day of sponge-hepatoc yte implantation (PCS + HEP), and the control group (CON) received no surgical stimulation. The sponges were vascularized by ingrowth of fib rovascular tissue over the first 7 days in vivo. Approximately 95-99% of the implanted hepatocytes (determined utilizing computer-assisted i mage analysis) died in all three experimental groups during this time. The number of engrafted hepatocytes in the CON group further decrease d over the next 7 days to 1.3 +/- 1.1% of the original cell number. Ho wever, the number of engrafted hepatocytes in the PCS and PCS + HEP in creased over this time to 6 +/- 1% and 5 +/- 2%, respectively. The num ber of engrafted hepatocytes in the PCS group continued to increase ov er the next 2.5 months to a value of 26 +/- 12% of the initial cell nu mber, and a large number of engrafted hepatocytes was still present at 6 months. These results indicate that stable new tissues can be engin eered by transplanting hepatocytes on biodegradable sponges into heter otopic locations if appropriate stimulation is provided. (C) 1997 John Wiley & Sons, Inc.