Human liver bud derived from human-induced pluripotent stem cells. Picture by Takanori Takebe

New Delhi, July 4: Scientists have for the first time used stem cells to grow a functional human organ, a liver generated from a rudimentary bud transplanted into mice where it matured into tissue resembling adult liver.

Japanese scientists have described their experiments as a “proof of the concept” that entire three-dimensional human organs for transplantation may be grown from stem cells, a class of progenitor cells that may turned into any type of body tissue.

The researchers at the Yokohama City University generated the liver buds from human-induced pluripotent stem cells (iPSC), cells reversed into a progenitor state.

The scientists created a cocktail of these iPSC with other types of cells and observed that they self-organise into a liver bud, a tissue that emerges in the early stage of development — in humans, at about five or six weeks of gestation. The experimental findings were described in the journal Nature on Thursday.

“This self-assembly to form a 3-D human liver bud was unexpected, (something) beyond our imagination,” Takanori Takebe, a research team member told The Telegraph. “The cells mimic normal (human) organ development process.”

When the scientists implanted these liver buds into mice, they developed into liver-like tissue with blood vessels and displayed some of the functions — such as the production of specific proteins — that the human liver performs.

But the scientists have cautioned that several research bottlenecks are yet to be overcome and it could take another seven to 10 years before the technology becomes advanced enough to begin clinical evaluation in human patients.

“This is significant, the first time 3-D organ-like structures have been created from pluripotent stem cells,” said Yashoda Ghanekar, a senior scientist with the National Centre for Biological Sciences, Bangalore, who was not associated with the study.

“They seem to have identified the niche, the precise cellular environment, to turn the stem cells into bud-like organs,” Ghanekar said. “But it is yet to be shown that these organs behave exactly as real human livers.”

Takebe said another key bottleneck would be to find ways to increase the amount of liver bud to make sufficient concentrations for use in humans. “The liver is a large organ and contains more than 10 billion hepatocytes (liver cells),” Takebe said. “We’ll have to produce significant amounts of liver bud at a reasonable cost and evaluate them for safety (for applications in humans).”

The Japanese scientists implanted the liver buds into the heads of mice because, they said, it was easier to monitor how the transplanted tissue behaves in the head than at the site of the liver.

A senior scientist at the University of Edinburgh cautioned that the liver buds do not contain the biliary structures or immune cells that characterise the real human liver.

“Although exciting, there is still a lot more research needed before this approach could be applied to patients with liver disease,” Stuart Forbes, professor of regenerative medicine at the University of Edinburgh, said in a release.