Researchers create miniature human liver out of stem cells

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Scientists have created a tiny liver from stem cells that helped mice with chronic liver failure regain function.

Researchers in Japan transplanted 4-millimeter-wide "liver buds" made from human stem cells into a mice. The transplanted liver buds, which were placed in the cranium or abdomen, were able to work in conjunction with the mice's own organs and secrete human liver-specific proteins. They also created human metabolites, tiny molecules that are produced when the body metabolizes a substance.

Co-author Takanori Takebe, a stem-cell biologist at Yokohama City University in Japan, said to Nature this was the first time people have made a solid organ using pluripotent stem cells, which are mature skin cells that are re-programmed to become an embryonic cell that can express any genetic characteristics.

In this case, the liver buds were made from pluripotent stem cells that were told to express liver genes. Endothelial cells (which line blood vessels) taken from umbilical chord blood and mesenchymal stem cells (which make bone, cartilage and fat) were put into the mix as well.

"We just simply mixed three cell types and found that they unexpectedly self-organize to form a three-dimensional liver bud -- this is a rudimentary liver," Takebe explained to the BBC. "And finally we proved that liver bud transplantation could offer therapeutic potential against liver failure."

After hundreds of trials, the three cells worked together and began to make three-dimensional structures. Takebe admitted he was "absolutely surprised" when he saw it working.

According to the Organ Procurement and Transplantation Network, there are currently more than 16,500 people registered on the liver transplant waiting list. There were only 6,256 people who received a liver transplant in 2012.

Takebe said that human transplantation is still years away, and the research is very preliminary. The mice still need be observed to see if the liver buds continue to function or tumors start to form. Also, the liver buds will never be able to grow into a full liver, but they could one day work with a failing liver and help restore its function. He hopes in the future researchers can create liver buds small enough to be transfused intravenously, and forsees that this method could also be used to create new pancreas or kidney cells.

"The real breakthrough here is that the tissues revascularized, growing new blood vessels, after being implanted," Alejandro Soto-Gutierrez, a researcher with the Center for Innovative Pediatric Regenerative Therapies in Pittsburgh who was not involved with the study, said to USA Today. "That's amazing, a very good result."

The research was chronicled in a Nature letter published on July 3.

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