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Liver stem cells grown in culture, transplanted with demonstrated therapeutic benefit

Date:
February 25, 2013
Source:
Oregon Health & Science University
Summary:
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 Papé Family Pediatric Research Institute at Oregon Health & Science University Doernbecher Children's 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.
Credit: Image courtesy of Oregon Health & Science University

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.

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In the journal Nature, physician-scientists in the Papé Family Pediatric Research Institute at Oregon Health & Science University Doernbecher Children's 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 Papé Family Pediatric Research Institute at OHSU Doernbecher Children's 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 Papé 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.


Story Source:

The above story is based on materials provided by Oregon Health & Science University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Meritxell Huch, Craig Dorrell, Sylvia F. Boj, Johan H. van Es, Vivian S. W. Li, Marc van de Wetering, Toshiro Sato, Karien Hamer, Nobuo Sasaki, Milton J. Finegold, Annelise Haft, Robert G. Vries, Markus Grompe, Hans Clevers. In vitro expansion of single Lgr5 liver stem cells induced by Wnt-driven regeneration. Nature, 2013; 494 (7436): 247 DOI: 10.1038/nature11826

Cite This Page:

Oregon Health & Science University. "Liver stem cells grown in culture, transplanted with demonstrated therapeutic benefit." ScienceDaily. ScienceDaily, 25 February 2013. <www.sciencedaily.com/releases/2013/02/130225153130.htm>.
Oregon Health & Science University. (2013, February 25). Liver stem cells grown in culture, transplanted with demonstrated therapeutic benefit. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2013/02/130225153130.htm
Oregon Health & Science University. "Liver stem cells grown in culture, transplanted with demonstrated therapeutic benefit." ScienceDaily. www.sciencedaily.com/releases/2013/02/130225153130.htm (accessed October 25, 2014).

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