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Novel liver stem cell model could speed up process for developing new drugs

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But now a research team reports that it has developed a way to speed up the process. Their work, which involves the creation of a highly stable and sensitive liver stem cell model, is reported in the latest issue of STEM CELLS Translational Medicine.

“Liver toxicity is the second most common cause of human drug failure,” explained David Hay, Ph.D., of the University of Edinburgh’s MRC Centre for Regenerative Medicine, who led the team made up of university colleagues and scientists from Bristol-Myers Squibb, Princeton, N.J. “But one major bottleneck in safety testing new drugs has been finding a routine supply of good quality primary human hepatocytes from the desired genetic background.”

Scientists have long believed that finding an efficient way to force pluripotent stem cells (PSCs) to develop into hepatocytes — liver cells — could be the way around the problem. “But faithfully recapitulating human physiology in a dish from a renewable source remains a holy grail for medicine and the pharmaceutical industry,” Dr. Hay noted.

“Many procedures have been described that, to a limited extent, exhibit human-tissue-specific function in vitro but incomplete cellular differentiation and/or the loss of cell phenotype after they differentiate. Using our knowledge in pharmacology, stem cell biology and materials chemistry, we developed a highly stable and sensitive model.”

Their method involved expanding PSCs and driving their differentiation to hepatocytes, then replating them onto a synthetic surface. The results yielded active cell populations that displayed stable function for over two weeks in vitro.

“The scalable nature of our model combined with the interchangeable genetic element demonstrates clear advantages over the erratic supply of highly variable human hepatocytes from deceased specimens,” Dr. Hay added. “We believe our approach is important and will likely contribute to improvements in drug safety testing.”

“This model was compared to human liver cells from deceased donors and found to be equivalent, suggesting that stem cell-derived hepatocyles have potential to improve the preclinical assessment of human liver toxicity,” said Anthony Atala, M.D., Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “