Liver grown from stem cells

In a world first, a functioning liver has been grown from stem cells by scientists in Japan.
04 July 2013

Liver buds

Human iPSC-derived liver bud.


In a world first, a functioning liver has been grown from stem cells by scientists in Japan...

Thousands of livers are transplanted each year, but many patients sadly still die before a suitably matched organ can be found.

Now scientists have taken the first steps down a road that could see doctors using a person's own cells to grow a replacement liver. Yokohama City University scientist Takanori Takebe and his colleagues used human skin cells that were first reprogrammed to turn them into iPS or induced pluripotent stem cells.

Incubating these cells in a culture dish in a cocktail of growth factors and alongside a second population of blood-vessel-forming stem cells, enabled the researchers to mimick the environment that triggers the liver to form in the early embryo.

The result was a ball of cell resembling the "liver bud" that gives rise to the future liver. Tests on the growing tissue showed that it was producing chemical markers and patterns of gene activity characteristic of mature liver cells.

Implanted into test mice, the liver buds quickly plumbed themselves into the local blood supply and continued to develop. Examined under the microscope two months later, the tissue structurally resembled mature liver, and was producing high levels of albumin, an essential blood protein, 45 days after implantation.

In a further test of the tissue's function, the researchers also administered to their test mice drugs that are metabolised differently by human and mouse livers. Blood samples collected subsequently showed human-specific metabolites, proving that the implanted liver tissue was working.

The team also tested whether their replacement livers could replace an animal's own organ. By implanting their human liver replacement tissue into mice genetically programmed to develop failure of their own livers, the Japanese team were able to show survival rates three times higher than in control animals that did not receive replacement liver tissue.

In concluding their paper, published in Nature this week, the scientists say, "our study demonstrates proof-of-concept that organ-bud transplantation offers an alternative approach to the generation of a three-dimensional vascularised organ. These results highlight the enormous therapeutic potential using in vitro-grown organ-bud transplantation for treating organ failure."


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