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The Scientist 14[23]:20, Nov. 27, 2000 http://www.thescientist.com/yr2000/nov/research_001127.html Liver Goal: To develop a plentiful source of hepatocytes for regenerating damaged livers and treating some metabolic diseases. Another functional stem cell is the hepatocyte. "For liver repopulation purposes and transplantation, the best cell type is the differentiated hepatocyte," says Markus Grompe, a professor of molecular and medical genetics and pediatrics at Oregon Health Sciences University. He adds that in transplants, hepatocytes are "far superior" to liver stem cells, whose existence has been established only in the past 12 months or so. The major source of hepatocytes for therapeutic purposes, however, is human cadavers. More accessible and plentiful are the liver stem cells residing in the bone marrow, discovered by Neil D. Theise, an associate professor of pathology at New York University School of Medicine, and colleagues. Their proof: The Y chromosome pops up in some hepatocytes after male marrow transplants into females. Are these new liver cells functional? In a small-scale study of human transplants,16 "We show such extensive engraftment that it's hard to avoid the conclusion that this is a part of physiological regeneration," asserts Theise. The next test is to use bone-marrow transplants to correct defective liver function in animal models of some human metabolic diseases. Grompe and a team of researchers published a paper this month reporting such a finding in a mouse model of tyrosinemia.17 The roles played by ASCs in the liver are still far from clear. Intrahepatic oval cells have recently--and grudgingly--won full acceptance as stem cells, particularly after injury. (Theise proposes that oval cells ultimately derive from the bone marrow.) Apparently no one has yet generated liver cells from ESCs. The growth factors "are just absolutely not known," notes Grompe. *********************