Next, they chemically induced the iPSCs to differentiate first into immature and then more mature liver cell types. Regardless of their origin, the different iPSC lines all showed the same ability to develop into liver cells.

Using mice with humanlike liver cirrhosis, the researchers then injected the animals with either two million human iPSC-derived liver cells or with normal human liver cells. They discovered that the iPSC-derived liver cells engrafted to the mouse liver with an efficiency of eight to 15 percent, a rate similar to the engraftment rate for adult human liver cells at 11 percent.

Researchers also found the engrafted iPSCs worked well. The scientists detected proteins normally secreted by adult human liver cells, including albumin, alpha-1-antitrypsin, transferrin and fibrinogen, in the blood of mice transplanted with human iPSC- derived liver cells.

Additional studies will need to be completed before clinical trials can begin, Jang says. One concern has been the potential for embryonic stem cells or iPSCs to cause tumors, though no tumors formed in any of the transplanted mice during the seven months they were studied (equating to more than 30 years in a human life). The scientists also plan to evaluate the impact of molecular memory that may linger in iPSCs for other type of cellular fate changes.

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