To find new cures, scientists need the right tools. A Doernbecher discovery is equipping researchers to develop new therapies for genetic disorders.
One of the most exciting frontiers in science today is cell therapy, which aims to cure diseases by replacing missing or damaged cells with healthy ones. Cell transplantation may offer new hope for children with sickle cell disease, inherited immune deficiencies, metabolic disorders, and other genetic diseases.
But the field is still fraught with challenges. One of the biggest obstacles is obtaining healthy cells suitable for transplantation. Markus Grompe, M.D., Doernbecher’s Ray Hickey Chair for the Director of the Papé Family Pediatric Research Institute, is on the verge of removing this hurdle – and is transforming what is possible in cell research.
Grompe’s research focuses on liver cell transplantation for genetic diseases. One such disease is MSUD (maple syrup urine disease), a rare metabolic disorder in which malfunctioning liver cells fail to produce a critical enzyme needed to break down protein in the body. If untreated, MSUD damages the nervous system, causing mental retardation. Newborns in Oregon are screened for MSUD, and those who test positive must be put on a severely restricted diet to control the disorder’s devastating effects. Right now, there is no cure.
“The hope for cell therapy is that it would lead to a lifelong correction of such disorders,” says Grompe, who also serves as director of the Oregon Stem Cell Center. Cell therapies work by introducing healthy cells that take over for damaged cells and permanently restore proper cell function. Bone marrow transplantation is one example of cell therapy. “In the case of MSUD or similar genetic liver disorders,” says Grompe, “one could imagine transplanting liver cells to correct the underlying problem. But the question is: Where do you get those liver cells?”
Cells in short supply
The shortage of viable liver cells has been a huge impediment to the advancement of cell therapy. Many liver cells available for research are poor-quality or nonviable, coming primarily from cadavers. High-quality livers are needed for organ transplants. An additional challenge is that mature liver cells do not divide and multiply in the laboratory, and sufficient quantities cannot yet be grown from stem cells.
To speed the pace of progress in research, Grompe and his team have developed a new way to produce transplantable liver cells consistently. And they’re well on their way to producing quantities large enough for developing and testing cell therapies.
“We have figured out a way to take those hard-to-get liver cells and expand them significantly by transplantation into animals,” says Grompe. The key is a genetically modified breed of mouse that Grompe’s team has engineered to accept and grow the human cells. “The reason it works to grow human liver cells in a mouse but not in a petri dish is that the cells are getting all the cues and instructions from the living organism that allow them to expand,” says Grompe.
A shared resource for science
Grompe founded Yecuris, an OHSU biotech startup, to commercialize this discovery and is now making the liver cells available to scientists and pharmaceutical researchers nationwide. In his quest to find new cures for kids, Grompe has developed a much-needed resource that is already benefiting other important avenues in medical research, including pharmaceutical testing.
“Our ultimate goal is cell therapy,” he says, “but in the meantime scientists are using these mice with human livers to study liver disease, such as hepatitis B and C. They’re also being used to study malaria, which affects millions of children and adults worldwide.”
“This approach is truly innovative,” says H. Stacy Nicholson, M.D., M.P.H., Doernbecher’s physician-in-chief. “Dr. Grompe and his group are world leaders in this methodology. Nobody has been able to do what they have done.”