The Potential of Stem Cell Transplantation to Rescue the Failing Liver
The growing shortage of donor organs calls for new approaches in organ transplantation. Hepatocyte transplantation in animal models has revealed the possibility to repopulate a damaged liver with normal liver cells. After injection into the portal vein, hepatocytes become correctly integrated into liver cell plates and are able to divide and perform a number of functions. Interestingly, transplanted hepatocytes become polarized and are able to secrete solutes and metabolites into bile. For instance, mdr 2 -/- knock out mice lack an essential canalicular phospholipid transporter and develop severe liver disease in particular upon feeding a bile salt supplemented diet. Under these conditions they produce a bile acid-rich phospholipid-poor bile that is toxic to hepatocytes and cholangiocytes. Syngeneic mouse hepatocytes containing either wild type mouse mdr2 or transgenic human MDR3 were transplanted into the livers of these mdr 2 -/- mice and were shown to partly repopulate the liver. After transplantation the knock-out mice produced phospholipid-containing bile and appeared protected from ongoing liver damage . This experiment proves several points: healthy hepatocytes transplanted into a damaged liver divide and partly repopulate the liver, the transplanted cells do not form clumps of hepatocytes not connected to the biliary tree but they integrate into the liver cell plates with a correct anatomical orientation so that they can perform the critical function of bile secretion.
KeywordsBone Marrow Cell Glycogen Storage Disease Intrahepatic Cholestasis Severe Liver Disease Fetal Liver Cell
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