New mouse research in Nature raises hope that human liver    stem cells can be similarly grown, transplanted  
    For decades scientists around the world have attempted to    regenerate primary liver cells known as hepatocytes because of    their numerous biomedical applications, including hepatitis    research, drug metabolism and toxicity studies, as well as    transplantation for cirrhosis and other chronic liver    conditions. But no lab in the world has been successful in    identifying and growing liver stem cells in culture -- using    any available technique  until now.  
    In the journal Nature, physician-scientists in the Pap Family    Pediatric Research Institute at Oregon Health & Science    University Doernbecher Childrens Hospital, Portland, Ore.,    along with investigators at the Hubrecht Institute for    Developmental Biology and Stem Cell Research, Utrecht,    Netherlands, describe a new method through which they were able    to infinitely expand liver stem cells from a mouse in a dish.  
    This study raises the hope that the human equivalent of these    mouse liver stem cells can be grown in a similar way and    efficiently converted into functional liver cells, said Markus    Grompe, M.D., study co-author, director of the Pap Family    Pediatric Research Institute at OHSU Doernbecher Childrens    Hospital; and professor of pediatrics, and molecular and    medical genetics in the OHSU School of Medicine.  
    In a previous Nature study, investigators at the Hubrecht    Institute, led by Hans Clever, M.D, Ph.D., were the first to    identify stem cells in the small intestine and colon by    observing the expression of the adult stem cell marker Lgr5 and    growth in response to a growth factor called Wnt. They also    hypothesized that the unique expression pattern of Lgr5 could    mark stem cells in other adult tissues, including the liver, an    organ for which stem cell identification remained elusive.  
    In the current Nature study, Grompe and colleagues in the Pap    Family Pediatric Research Institute at OHSU Doernbecher used a    modified version of the Clever method and discovered that    Wnt-induced Lgr5 expression not only marks stem cell production    in the liver, but it also defines a class of stem cells that    become active when the liver is damaged.  
    The scientists were able to grow these liver stem cells    exponentially in a dish  an accomplishment never before    achieved  and then transplant them in a specially designed    mouse model of liver disease, where they continued to grow and    show a modest therapeutic effect.  
    We were able to massively expand the liver cells and    subsequently convert them to hepatocytes at a modest    percentage. Going forward, we will enlist other growth factors    and conditions to improve that percentage. Liver stem cell    therapy for chronic liver disease in humans is coming, said    Grompe.  
    The study, In vitro expansion of single Lgr5+ liver stem cells    induced by Wnt-driven regeneration, was funded by National    Institutes of Health Grant R0I DK05192.  
    Investigators who contributed to this research include: Grompe,    Craig Dorrell, Annelise Haft, Pap Family Pediatric Research    Institute, OHSU Doernbecher Childrens Hospital; Clever,    Meritxell Huch, Sylvia Boj, Johan van Es, Vivian Li, Mare van    de Wetering, Toshiro Sato, Karien Hamer, Nobuo Sasaki, Robert    Vries, Hubrecht Institute for Developmental Biology and Stem    Cell Research; and Milton Finegold, Texas Childrens Hospital    Houston.  
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OHSU Doernbecher Scientists First To Grow Liver Stem Cells In Culture, Transplant Them With Demonstrated Therapeutic ...