Experimental Study On The Effect Of Allograft Hepatocyte Transplantation On Liver Fibrosis In Rat

Hepatocyte transplantation (HTx) has been evaluated as a less invasive alternative to organ transplantation or as a "bridge" for patients who are waiting for a donor liver. It has been shown to improve the survival of animals experimentally induced with acute liver failure, decompensated cirrhosis, or even anhepatic. However thus far, compared with the emphasis placed on study of other liver diseases, the therapeutic potential of HTx for the treatment of the most common characteristic of chronic liver diseases—fibrosis—has not been studied carefully. Although it is well known that if left unmanaged, fibrosis has serious long-term consequences for morbidity and mortality.Additionally, despite several recent encouraging clinical trials of HTx for the treatment of acute liver failure and metabolic liver disease, the clinical reality has lagged behind theoretical promise. One of the important reasons is the mechanism of HTx has not been totally understood. We performed the present study to answer, or at least to obtain some insights into those questions which might potentially increase the safety and effectivity of HTx and eventually make it a universal use in the field of clinical.Herein, we report that intrasplenic allograft HTx can promote the reversal progress of liver fibrosis in rat. The inactivation of the hepatocyte stellate cell (HSC) and decrease in transforming growth factor-beta I(TGF-β1) byα2-macroglobulin-plasmin complex may play an important role during this process.Aim To investigate the effect of allografted hepatocyte transplantation (HTx) on the progress of liver fibrosis in rat.Methods Cells labeled with CM-DiI fluorescence were transplanted into male Wistar rats with or without liver fibrosis. Nonlinear optical microscopy was used to image the distribution of collegen within the liver tissue. The quantification of liver fibrosis was assessed by computerized image analysis. To observe the effect of HTx on the progress of liver fibrosis, another group of rats with liver fibrosis were recovered spontaneously as control. Immunohistology ofα-smooth muscle actin (α-SMA) was used to investigate the activation status of hepatic stellate cells (HSCs). Active and total TGF-β1, plasmin andα2-Macroglobulin (α2M) in plasma were measured by ELISA because of their critical role in the progress of liver fibrosis.Results Two weeks after ceasing of CC14 injection, the liver fibrotic area in the rat that underwent HTx was significantly less than that in the spontaneous recovery group (3.69±0.44 vs. 8.25±0.69, P＜0.01). Also, one day after HTx, both of total and active TGF-β1 level reduced dramatically. The level of plasmin andα2M also changed significantly before and after the HTx respectively.Conclusions HTx can benefit the reversal of liver fibrosis in rat. The inactivation of HSCs and the internalization of TGF-β1 by hepatocytes in the presence of plasmin andα2M may ultimately responsible for this event.