A rudimentary human liver from stem cells

Stem-cell success: Three cell types when mixed unexpectedly self-organised to form 3D liver bud — a rudimentary liver. Photo: Takanori Takebe  

In what is likely to be an important step towards regenerating complex organs from a person's own cells, a team of Japanese scientists has used reprogrammed stem cells to produce a rudimentary human liver that could function in mice.

The research could, in time, find clinical application as a way to help those with life-threatening liver damage, according to Takanori Takebe of the Yokohama City University Graduate School of Medicine in Japan. He is the first author of a paper on this work published today (July 4) in Nature.

Their approach could be utilised for making other organs like pancreas, kidneys and lungs, said Prof. Takebe during a telephone press briefing organised by the journal.

The Japanese scientists began with ‘induced pluripotent stem cells’ (iPS cells) created by introducing certain genes into mature human cells. Like embryonic stem cells, iPS cells too can differentiate into all the various cells that make up the body.

First, the human iPS cells were turned into progenitor liver cells. The progenitor cells were then cultured in a dish along with two other sorts of cells that interact with each other during the liver's embryonic development.

“We just simply mixed three cell types, including the human iPS-derived hepatic progenitors, and found that they unexpectedly self-organise to form a three-dimensional liver bud — [which] is a rudimentary liver,” remarked Prof. Takebe during the briefing.

In human embryonic development, the liver bud normally forms five or six weeks after gestation. “We basically mimicked this very early transition process,” he said.

The human liver buds were then implanted in mice, and cells in those buds continued to proliferate vigorously. Blood vessels that had developed in the buds rapidly connected with those of the host animal.

The proof

When given drugs that human and mice livers break down differently, human metabolic residues were detected in the blood and urine of mice with liver buds. The buds also helped mice with chemically-induced liver failure survive, the scientist reported in their paper.

This study highlighted how cues from cells of different types were important in directing the genesis of organs, observed Indumathi Mariappan, a researcher at the L.V. Prasad Eye Institute in Hyderabad who works with iPS cells.

Rather than being used to generate whole livers, the immediate clinical application that Prof. Takebe foresees for the technique is of at least partially restoring the function of a badly damaged one. For this, large numbers of buds could be infused into such a liver through a blood vessel.

For that, the liver buds would have to be very much smaller than at present and must be produced in vast numbers, he said. It could be another 10 years before such a method is ready for clinical trials in humans.

According to him, his team is working on making pancreas in this fashion, and has been getting good results so far.

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Printable version | Oct 22, 2020 6:14:20 AM |

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