Researchers report in Hepatology that this technique could aid drug toxicity testing.

Scientists report that they have created functional liver cells from adult skin cells using an induced pluripotent stem cell (iPSC) technology. The researchers at the University of Edinburgh’s MRC Centre for Regenerative Medicine and Harvard Medical School suggest the technology could be used to generate an unlimited supply of hepatocytes for drug toxicity testing as well as off-the-shelf models of human liver disease.

The team says that this is the first successful application of iPSC technology to transform adult skin cells into liver cells. Their research is published in Hepatology in a paper titled “Generation of functional human hepatic endoderm from human iPS cells.”

The scientists used iPSC technology to create hepatic endoderm, which was then differentiated into hepatocytes. They claim that the in vitro-derived hepatocytes show similar attributes to those of primary human hepatocytes (PHHs) derived from dead or donor tissue. PHHs are currently the gold standard cell type used for predictive drug toxicology.

The iPSC technique was also successful in using a variety of polymorphic variants, with cells derived from males and females of different ethnic origin.

“iPSC-derived hepatic endoderm exhibited hepatic morphology and expressed the hepatic markers albumin and E-cadherin as assessed by immunohistochemistry,” the authors note. “They also expressed alpha fetal protein (AFP), HNF4a, and a metabolic marker Cyp7A1, demonstrating a definitive endodermal lineage differentiation.

“Furthermore, iPSC-derived hepatocytes produced and secreted the plasma proteins, fibrinogen, fibronectin, transthyretin, and AFP, an essential feature for functional hepatic endoderm. Additionally iPSC-derived hepatic endoderm supported both CYP1A2 and 3A4 metabolism, which is essential for drug and toxicology testing.”

“We are now looking for ways to bring this technology into routine use for drug testing,” says Sir Ian Wilmut, Ph.D., director of the Centre for Regenerative Medicine and one of the paper’s co-authors.


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