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article imageFunctional liver made from stem cells for the first time

By Kathleen Blanchard     Jul 4, 2013 in Science
Researchers in Japan have engineered functional human liver tissue from stem cells that they say could someday help remedy the critical shortage of organs needed for transplant.
The research is still in its infancy stages but has generated excitement among scientists for the future of regenerative medicine.
The researchers used a variety of stem cells to accomplish their goal of producing liver “buds” that were then transplanted either into the brains of mice or the abdomen.
The cells used are known as induced pluripotent stem cells or iPSCs, which are created by reprogramming mature cells to turn into an embryo-like state where they can be then be made to differentiate into any type of body cell.
Shinya Yanamaka who received the Nobel Prize in 2012, first discovered how to eliminate the use of embryonic stem cells to treat human diseasethat generated much controversy.
Valerie Gouon-Evans, who studies liver development and regeneration at Mount Sinai Hospital in New York, said “This is a very novel thing. Because the liver buds are supported by the host’s blood system, transplanted cells can continue to proliferate and perform liver functions”, reported Nature.com.
One of the problems with pluripotent stems cells is their propensity to develop tumors. Gouon-Evans explains mice used in the current experiment will have to be watched for several months for the development of cancer.
In the experiments the stem cells attached to blood vessels and continue to grow after transplantation, taking on a variety of liver functions that prevented the mice from dying of liver failure.
Takanori Takebe, a stem-cell biologist at Yokohama City University in Japan who co-led the study said human treatments are still years away. It is also still impossible to make enough liver buds to transplant in humans.
Takebe hopes to make liver but small enough to deliver intravenously in mice and then eventually in humans. Injecting stem cells directly into the liver could potentially form bile ducts for proper digestion.
The researchers used to three types of human cells to create liver buds that are approximately 4 mm across, coaxing the cells to produce liver genes in the lab. Then they added skin (epithelial) cells that form blood vessels, derived from umbilical cord blood; followed by mesenchymal stem cells that form bone, fat and cartilage. The combination mimics liver formation in the developing embryo.
Takebe said it took hundreds of trials to find the right combination of cells that would self-organize into three dimensional liver buds.
Kenneth Zaret, called the breakthrough “…a great day for developmental biology.” Zaret studies regenerative medicine and liver development at the University of Pennsylvania in Philadelphia.
The study authors write, “Although efforts must ensue to translate these techniques to treatments for patients, this proof-of-concept demonstration of organ-bud transplantation provides a promising new approach to study regenerative medicine.”
More about liver buds, Stem cells, Takanori Takebe, Yokohama City University
 
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