Stem cells grown into functional human livers

Functional miniature human livers have been created from induced pluripotent stem cells, say Japanese researchers in a study published today in the journal Nature. (Click link to read study).

Called "liver buds", these mini-livers metabolized drugs in a human fashion, and performed most other functions of a liver, the researchers said. Moreover, the implanted livers prolonged survival of mice with chemically induced liver failure, as compared to control mice given a sham operation.

The researchers used a new method to create the liver buds, grown on glass slides. They surrounded the nascent liver tissue with two other cell types that supported formation of the buds, including human umbilical vein endothelial cells. These cells self-organized and created their own blood vessels. When implanted, the liver buds hooked up to the mouse circulatory system.

"Notably, although cells were plated in two-dimensional conditions, human iPSC-HEs (liver cells grown from IPS cells) self-organized into macroscopically visible three-dimensional cell clusters by an intrinsic organizing capacity up to 48 (hours) after seeding," the paper stated.

Takanori Takebe, of Yokohama City University Graduate School of Medicine, is the paper's first author. The senior author is Hideki Taniguchi, also of the university.

Other organs such as kidneys can be produced by the bud process, Takebe said in a press conference Tuesday. However, it will take about 10 years before the method is ready for human clinical trials.

The mini-livers do most of the liver's important biochemical functions, but not bile production, Takebe said.

The paper "presents some exciting proof-of-concept evidence that offers potential solutions to current limitations in the fields of stem cell biology, tissue engineering and their clinical application," said Gail Naughton, a San Diego regenerative medicine pioneer. "Such limitations to current tissue engineered grafts include the need to use a 3D biomaterial as a scaffold and to provide an immediate blood supply," Naughton said in an email.

"Of exciting clinical significance is the fact that the new liver was able to rescue mice that were in a chemically induced liver failure," said Naughton, CEO of San Diego-based Histogen, which is clinically testing a hair regeneration technology.

Earlier in her career, Naughton founded Advanced Tissue Sciences, a now-defunct San Diego company. There, she guided development of a living human skin substitute called DermaGraft, now produced in San Diego by Shire Regenerative Medicine. However, the company's experiments in growing more complex organs, such as liver, were unsuccessful.

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Stem cells grown into functional human livers