A team of researchers led by Dr. Stephen Duncan at the Medical College of Wisconsin recently discovered what is likely to be the next critical advancement in developing stem cell therapy for human beings.
Duncan’s team utilized molecular genetics to successfully produce liver cells from a patient’s skin cells, in hopes of creating therapies to treat liver disease.
According to Duncan, the team took the selected human skin cells, “reprogrammed” them to be stem cells and then turned the stem cells into liver cells.
“We could trick them to become liver cells,” said Duncan. “In mice, the cells were capable of making human liver proteins.”
Duncan is a program director in regenerative medicine and stem cell biology and is the Marcus Professor in Human and Molecular Genetics at the Medical College. He led graduate students Fallon Noto and postdoctoral fellow Karim Si-Tayeb in doing the liver cell research.
The Medical College research team first repeated the work of James Thompson and colleagues at the University of Wisconsin-Madison, who showed that skin cells can be reprogrammed to become cells that resemble embryonic stem cells.
“This has been a big team effort to do aspects of this project,” said Duncan.
He credits Noto with generating the cell types to make the IPS cells and Si-Tayeb with changing the embryonic cells into liver cells.
“It is like putting a jigsaw puzzle together to come up with the complete puzzle to move the study together,” Duncan said.
Previous studies have shown that liver cells generated from embryonic stem cells could potentially be used for therapy. According to Duncan, due to the current medical climate and the ongoing debate about the use of human embryonic stem cells (hESC), the team chose to work with skin cells.
On March 9, 2009, President Barack Obama issued an executive order removing barriers to responsible scientific research involving human stem cells, supporting scientific-worthy human stem cell research, including (hESC) research to the extent permitted by law. The National Institute of Health (NIH) issued new guidelines in July 2009 for human stem cell research.
Liver disease is the fourth-leading cause of death among middle-aged adults in the United States. In the most severe cases, liver transplants are used to treat liver disease. According to the Scientific Registry of Transplant Recipients, in 2008 there was a 39 percent transplant rate for patients on the transplant list.
Duncan’s team is continuing its investigation into creating therapies to treat liver disease. He outlined the current two-phase task of developing a drug therapy to treat liver disease. The first is to take skin punch biopsies and start to make stem cells from protein cells and see if they can find a drug to reverse disease states. The second is to utilize mice to see if they could reverse the disease with the identified drug set.
“We would like to start examining liver cells,” he said. “If we could pre-test and take your skin punch biopsy – if given combinations, it could tailor a series of drugs.”
Duncan said that he has talked to several pharmaceutical companies about possible drug combinations. He said that previous experimental drugs to treat liver disease were later taken off the market by the U.S. Food and Drug Administration (FDA) in speculation that they were causing more harm to the organ.
“The liver is the main organ that detoxifies. It is like a sponge that takes up compounds and could get damaged,” said Duncan.
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Duncan’s interest in liver disease started during his postdoctoral work at Rockefeller University in New York under one of the “grandfathers” of molecular biology, Dr. James Darnell, where Duncan worked to identify the proteins that composed liver cells in mice. Duncan joined the Medical College in 1997, started his own lab and expanded his work from Rockefeller University.The Program in Regenerative Medicine and Stem Cell Biology was created at the Medical College in 2007 with assistance from the Dr. James Guhl Memorial Fund, the Marcus Family, the Phoebe R. and John D. Lewis Foundation, the Sofia Wolf Quadracci Memorial Fund for Stem Cell Research and federal programs from the state of Wisconsin and the NIH.
