Realistic stem cell therapies to replace diseased or damaged tissue may still be years away, but researchers have uncovered a promising new use for these undifferentiated cells: they can be programmed to become patient-specific laboratory models of inherited liver disease. These new tools could be useful for teasing out disease mechanisms and testing new drug therapies.

Scientists from the University of Cambridge's Institute for Medical Research obtained skin cells from 10 patients—seven who had various forms of inherited liver disease, and three healthy controls. They reprogrammed the skin cells, rejuvenating them into an embryolike state (using the four-gene approach described in 2007). The researchers then cultured these so-called induced pluripotent stem cells (iPS cells) in a mixture of chemical factors that triggered their conversion into liver cells, which had the appearance and functional properties of native liver cells.

When the team compared three of the disease-specific cultures with the cells generated from the healthy controls, they discovered that the diseased cells had many of the key molecular defects characteristic of the original donors' liver disorder. An example comes from a patient with familial hypercholesterolemia—a disease that causes high blood levels of "bad" LDL (low-density lipoprotein) cholesterol because a cellular defect prevents the liver from absorbing LDL. The new liver cells created from this patient also lacked the proper machinery to take up LDL. Cultures representing two other hereditary liver diseases, alpha 1–antitrypsin deficiency (a protein-folding disorder that leads to cell death and liver failure) and glycogen storage disease, type 1a (in which a liver enzyme deficiency impairs the body's glucose metabolism), also displayed disorder-specific abnormalities.

The finding opens up ways to investigate malfunctioning livers. "One problem in liver research is that no one is able to grow liver cells in the lab," says the study's lead author, Sheikh Tamir Rashid. That inability, he explains, has made the mechanisms of different liver diseases difficult to understand. "Now it's going to be possible to ask at the level of the individual what is going on. We can then identify the right targets for therapeutic drugs," he adds.

This proof-of-principle study shows "for the first time…that human iPS cells can be used to model a diverse range of inherited diseases in adult cells," the authors wrote in their paper, published online in The Journal of Clinical Investigation August 25. They suggested that their approach could be used to study other, more common metabolic disorders. Ludovic Vallier, one of the paper's corresponding authors, said in a prepared statement: "Our work represents an important step towards delivering the clinical promises of stem cells."

Rashid's ultimate hope is that one day scientsts will be able to correct the diseased cells in the lab and transplant them back into the patient, but he cautions that cell-based therapies won't be available anytime soon. One problem with using iPS cells therapeutically is that the reprogramming process creates cells prone to forming tumors. Furthermore, regulations stipulate that each new cell line generated be independently tested and validated for safety, making it impractical to develop patient-specific cells for therapies. For now, Rashid's group has a list of candidate therapeutic drugs that they'll test in their new liver disease models, something that may still prove useful to patients.