This is a cool science story from Japan this week, reported in one of the top journals, Nature. Human stem cells formed little “liver buds” and when transplanted into lab animals, developed blood vessels and became functional.
From the published abstract
To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells. 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.
The research, from the lab of Takanori Takebe at Yokohama City University, was widely reported – be sure and see a news article from Nature
, or a good one from the New York Times
In a nutshell: Small liver buds, about the size of a pea, were formed from stem cells that started out as human skin cells. These are called induced pluripotent stem cells, or iPSC. These cells are deprogrammed, or rewound, so to speak, to a more primitive state, similar to an embryonic stem cell. The iPSC were then pushed toward a new fate, as a cell that expresses liver genes – not quite a liver cell but genetically coded as such. To get the buds to form a liver-type tissue, the science team added endothelial cells (from the lining of blood vessels) and some mesenchymal cells (from bone marrow, or adipose tissue).
After hundreds of tries, the team got the right blend of cells. To their surprise and joy, the cells figured out on their own how to form the liver buds. "They unexpectedly self-organize to form a three-dimensional liver bud — this is a rudimentary liver," Takebe said.
Once transplanted in mice, the buds began acting like livers — secreting liver-specific proteins and integrating with nearby blood vessels to continue growing. Mice that would have died because of liver failure were saved by the transplants.
While it sounds like the most likely potential clinical usefulness would be in the organ transplant realm (still years off -- the liver buds are far from ready to go) it is the lessons in developmental biology that make this science significant in the regenerative medicine realm. Liver restoration would of course be great for the thousands of people on the liver transplant waiting list, but beyond that…..there is great promise using iPSC to build tissue that can help screen drugs. And out a few more years, imagine if scientists can figure out exactly how a stem cell is assigned its fate; what if they can then manipulate that fate toward formation of all sorts of replacement tissue, including brain and spinal cord tissue.
Another interesting aspect to the story is the commitment Japan and its Prime Minister Shinzo Abe have made to iPSC development (recall that last year’s Nobel Prize for medicine was given to Japanese scientist Shinya Yamanaka, who isolated human iPSC in 2007). Just days before publication of this paper, a Japanese regulatory agency approved the first human trial of iPSC to treat macular degeneration, which can lead to blindness. This trial is part of the aggressive approach to iPSC in Japan, and is not without controversy. There are many questions that remain about iPSC, which can over-produce themselves (forming teratomas, or tumors).
From the Asahi Shimbun
, the second largest newspaper in Japan, an editorial called “Too much of a rush for clinical trials with iPS cells:”
What we find worrisome is the somewhat over-eager attitude of the Abe administration, which wants to make iPS technology one of the pillars of its economic growth strategy. But the safety of the technology, much less its effectiveness, has yet to be confirmed.
…. It is the role of the government to provide the right environment for research with a strong emphasis on safety and effectiveness. What it must not do is to be guided by economic motives.