A niche in the market
Other researchers have developed competing technologies using scaffolds to build three-dimensional liver-like structures. Sangeeta Bhatia, a bioengineer at the Massachusetts Institute of Technology in Cambridge, for example, has produced a scaffold-based graftthat doesn’t try to recapitulate development but has proved to be functional and transplantable in mice. Bhatia is now working on increasing the number of hepatocytes present on the two-centimetre graft, to ensure that it is useful in the clinic. "One billion cells is the next frontier," she says.
In the meantime, Takebe and the rest of the team, led by Hideki Taniguchi, also a stem-cell biologist at Yokohama City University — who are collaborating on the project with researchers at Sekisui Medical, a biotechnology firm based in Tokyo — hope that his liver bud could be useful for toxicity testing in drug screening, for which bile ducts are not needed. Many conventional hepatocyte cells that are transplanted to mice for in vivo testing last for only two or three days, but the drug and its various metabolites might take weeks to metabolize, so toxic effects might not be apparent in such testing. Takebe says his graft has the necessary staying power.
Many researchers are already growing hepatocyte-like cells: Bhatia, for example, has already commercialized a device that uses bioengineered cells for drug testing. However, Takebe’s liver bud has the advantage of being grown from iPS cells, rather than, for example, the primary human hepatocytes used in Bhatia's graft, which could make it useful in modelling rare diseases or examining the specific genetic backgrounds of the iPS cell donors.
Markus Grompe, who studies liver disease at the Oregon Health and Science University in Portland, says that Takebe's team is "on the right track”. Still, he says, the liver cells need to function much more efficiently than they do at present. On the basis of a cursory inspection of Takebe's data presented at the meeting, Grompe says that the liver bud was producing only a small fraction of the albumin — a plasma protein that is a key marker of liver function — that it should. But Takebe says that since his group generated the data presented at the Yokohama meeting, procedural improvements have already led to higher levels of albumin.
The next step for the team is to try to make the liver bud more liver-like, by including structures such as bile ducts.