The efficacy of prevascularization by basic FGF for hepatocyte transplantation using polymer devices in rats

Abstract

This study used polymer devices implanted in rats to investigate the effect of prevascularization by basic fibroblast growth factor (bFGF) on hepatocyte transplantation (HTx). Lewis rats served as both donors and recipients. Polyvinyl alcohol (PVA) sponges with either hydrogel containing bFGF (bFGF group) or distilled water (control group) were implanted between the mesenteric leaves of recipient rats. Hepatotrophic stimulation was induced by a portacaval shunt and a 70% partial hepatectomy. After 1 week of prevascularization, hepatocytes harvested from the donor Lewis rats using a collagenase digestive method were injected into the sponges. Specimens were harvested at 2 weeks, 1 month, and 2 months after HTx. Histologic examination revealed that the control groups contained small numbers of hepatocytes restricted to the peripheral areas of the sponges. However, a large number of hepatocytes, including clusters, was found distributed uniformly in the bFGF group. In the bFGF group at 2 weeks, 1 month, and 2 months, the percentage of the sponge occupied by hepatocytes was 7.21 ± 2.64%, 6.98 ± 2.59%, and 5.58 ± 3.77%, respectively. The corresponding ratios for the control group were 0.40 ± 0.39%, 0.40 ± 0.40%, and 0.87 ± 1.51 %. In addition, the mean number of new blood vessels in the bFGF group was significantly greater than that in the control group at 0 days, 2 weeks, and 1 month after HTx. These results suggest that bFGF strongly induced vascularization, which enabled a large number of hepatocytes to survive in the polymer devices.