Replacement of Diseased Mouse Liver by Hepatic Cell Transplantation

Abstract

Adult liver has the unusual ability to fully regenerate after injury. Although regeneration is accomplished by the division of mature hepatocytes, the replicative potential of these cells is unknown. Here, the replicative capacity of adult liver cells and their medical usefulness as donor cells for transplantation were investigated by transfer of adult mouse liver cells into transgenic mice that display an endogenous defect in hepatic growth potential and function. The transplanted liver cell populations replaced up to 80 percent of the diseased recipient liver. These findings demonstrate the enormous growth potential of adult hepatocytes, indicating the feasibility of liver cell transplantation as a method to replace lost or diseased hepatic parenchyma.

Cell cycle regulation and hepatocarcinogenesis

“…However, serial transplantation studies have demonstrated that hepatocytes can replicate many times if appropriately stimulated. [43][44][45] The earliest activating signals after partial hepatectomy initiate from Kupffer and endothelial cells within the liver 46 (Fig. 2).…”

Experiments in transgenic mice show that hepatocytes are the source for postnatal liver growth and do not stream*1

“…Additional support for the hypothesis that parenchymal hepatocytes have a high proliferative potential was obtained in an experiment where ~-gal expressing hepatocytes underwent up to 12 doublings after transplantation into a recipient mouse whose liver expressed a toxic transgene product. 41 These experiments suggest that mature hepatocytes have a tremendous proliferative potential, although the severely abnormal recipient liver may have altered the developmental pattern of the donor cells and the fact that less than 7% of the injected cells gave rise to nodules raised the possibility that rare stem cells and not parenchymal cells were the cells that proliferated extensively. Similarly, Chen et a142 noted that adult hepatocytes from either the periportal or the pericentral region were able to proliferate extensively after transplantation into the rat spleen, suggesting that all hepatocytes are capable of replication regardless of position in the liver.…”

Chondrocyte spheroids on microfabricated PEG hydrogel surface and their noninvasive functional monitoring

“…Indeed, the gelatin-coated gold circular domains, separated by PEGylated regions, substantially adsorb BSA as detected by immunofluorescence microscopy after treating with a FITC-conjugated anti-BSA antibody ( figure 4(b)). Note that the fluorescence image was well correlated with the results of surface elemental analysis, conducted by scanning electron microscopy with energy-dispersive x-ray spectroscopy (SEM-EDX) and x-ray photoelectron spectroscopy (XPS) experiments [29].…”