Bojian Jiang

Effects of Bone Marrow and Hepatocyte Transplantation on Liver Injury

BACKGROUND The therapeutic effects of bone marrow and hepatocyte transplantation were investigated regarding the treatment of retrorsine-partial hepatectomy-induced liver injury. METHODS Analbuminemic F344alb rats were given two doses of retrorsine 2 wk apart, followed 4 wk later by transplantation with F344 rat bone marrow cells or hepatocytes immediately after a two-thirds hepatectomy. The survival rate, liver regeneration rate, liver functions, albumin-positive hepatocytes, and normal albumin gene sequences in the liver and serum albumin levels were investigated in the recipients. RESULTS Although 65% retrorsine/partial hepatectomy-treated F344alb died between 1 and 11 d after the partial hepatectomy, only 27.5% of the animals died following bone marrow transplantation, and 50% with hepatocyte transplantation. Both bone marrow and hepatocyte transplantation ameliorated acute liver injury after a partial hepatectomy. Bone marrow transplantation yielded a very small increase in the number of albumin-positive hepatocytes in the liver, while hepatocyte transplantation resulted in massive replacement of the liver tissues by the donor hepatocytes associated with an elevation of serum albumin after an extended time. CONCLUSIONS Both bone marrow and hepatocyte transplantation could prevent acute hepatic injury, conceivably due to a paracrine mechanism.

Beneficial Effect of Hepatic Stimulatory Substances on the Survival of Intrasplenically Transplanted Hepatocytes

Intrasplenic hepatocyte transplantation has been demonstrated to have a tentative role in treating experimental liver disease, but methods for promoting the rapid proliferation of intrasplenic hepatocytes are still quite limited. In this study, hepatic stimulatory substances (HSS) obtained from regenerating porcine livers were injected directly into the subcutaneously translocated spleens of recipient rats that had received intrasplenic hepatocyte transplantation. The clusters of intrasplenic hepatocytes contained more than 100 cells, and formed cord structures at 2 wk after transplantation, and the hepatocytes still survived at 6 wk in the HSS-treated rats. In contrast, the clusters contained less than 10 hepatocytes at 2 wk after transplantation, and no surviving hepatocytes was observed at 4 and 6 wk in control rats. Additionally, marked proliferation of bile ductular-like structures appeared around the clusters of surviving hepatocytes in the splenic red pulp of the HSS-treated rats, but were not found in control rats at 4 and 6 wk after transplantation.

Proliferation and morphogenesis of biliary epithelial cells in syngeneic hepatocytes transplantation into the spleen under FK506

Abstract We have reported an in vivo system in which hepatocytes survice and proliferate in the rat spleen. Using this experimental approach, we observed that the systemic administration of FK506 induced the proliferation and morphogenesis of biliary epithelial cells in syngeneic hepatocytes transplanted into the spleen. This suggests that FK506 plays a crucial role in hepatocyte differentiation, or in the proliferation and morphogenesis of biliary epithelial cells.

Effects of monoclonal antibodies to ICAM-1 and LFA-1 on allogeneic hepatocytes transplanted into the rat spleen

Abstract To determine whether monoclonal antibodies (MAbs) against intracellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) can overcome the rejection of allogeneic transplanted hepatocytes in rat, we examined the effect of these MAbs on the survival of hepatocytes transplanted into the spleen between strains with a minor degree of histoincompatibility. We found that administration of these MAbs prolonged the survival of transplanted allogeneic hepatocytes. This finding suggests that some adhesion molecules play a role in the rejection of transplanted allogeneic hepatocytes in rats as well as of organ transplantation in mice.

Oxygenated Static Preservation of Donation after Cardiac Death Liver Grafts Improves Hepatocyte Viability and Function.

Background: Cell therapy, such as hepatocyte transplantation (HTx), is promising for the treatment of metabolic liver diseases or as a bridge to orthotopic liver transplantation in patients with fulminant liver failure. However, one of the limitations of this therapy is the shortage of donors. The present study aims to investigate whether the two-layer method (TLM) of cold preservation with oxygenation improves the viability and activity of hepatocytes from rat donation after cardiac death (DCD) donors compared with results obtained with the University of Wisconsin (UW) solution. Moreover, we evaluated the hepatocyte function after culture or transplantation into the spleen. Materials and Methods: We used male Sprague-Dawley rats for this study. The DCD model was induced by phrenotomy after injecting heparin. We assigned rats based on warm ischemia times of 15 and 30 min to groups S and L, respectively. Each group (n = 5) was then subdivided as follows: (1) group S: not preserved (S/N), preserved by TLM for 3 h (S/TLM3) and 12 h (S/TLM12), and in the UW solution for 3 h (S/UW3) and 12 h (S/UW12), and (2) group L: not preserved (L/N), preserved by TLM for 3 h (L/TLM3) and 12 h (L/TLM12), and in the UW solution for 3 h (L/UW3) and 12 h (L/UW12). The cell viability and function of isolated DCD hepatocytes were analyzed for culture or HTx into the spleen. Results: The viability and ATP levels of DCD hepatocytes significantly improved after TLM compared with the values after preservation in cold UW solution in group S/N (p < 0.059). The levels of albumin production and urea synthesis by hepatocytes after culture were significantly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12 (p < 0.05), respectively. Further, serum albumin levels after HTx were also markedly higher in groups S/TLM3 and S/TLM12 than in groups S/UW3 and S/UW12. The morphological features revealed that cultured and transplanted hepatocytes remained clearly viable and maintained an expression for specific hepatic function, such as the production of albumin and glycogen. Conclusion: This novel method of oxygenated cold preservation of DCD livers can expand the hepatocyte donor pool for HTx and establish a wider application of this developing technique.

F344-derived bone marrow cells restore injured liver with retrors ine poisoning and partial hepatectomy in analbuminemic rats

F344-derived bone marrow cells restore injured liver with retrors ine poisoning and partial hepatectomy in analbuminemic rats