The achievement represents a new direction in the use of human pluripotent stem cells, which have the potential to develop into any of the tissues of the human body. So-called induced pluripotent stem (iPS) cells, which are derived from adult human tissue, have the added advantage of producing tissues and organs genetically matched to a recipient, avoiding the problem of immune system rejection.
But creating fully mature human tissue in a petri dish (in vitro) has proved a daunting challenge, especially when it comes to producing 3D organs. Rather than do it all in a dish, the group decided to try starting the process in vitro but completing it in an animal (in vivo).
They tried hundreds of different recipes; eventually they discovered that if they mixed liver precursor cells (derived from iPS cells) with two other types of standard human cell lines known to be important for embryonic liver development, then the cells would spontaneously form a 4 to 5-millimeter 3D structure called a liver bud. "This worked beyond our expectations, though the mechanism is not entirely clear," says group leader and stem cell scientist Takanori Takebe of Yokohama City University in Japan.
Next, they implanted these buds in mice with disabled immune systems to see if they would engraft, or attach to the blood vessels of the animal, and continue to mature. They did: The transplanted liver buds developed into what Takebe calls "miniature livers." The team then confirmed that these tiny organs produced proteins typically made by human livers, and they properly processed certain drugs that mouse livers cannot handle.
The experiment shows that precursor cells can develop into functional organs when placed within the body of an adult mammal; it provides hope that even primitive tissues made from stem cells will one day restore the function of dead or diseased organs in patients. But there are significant hurdles to clear before the technique reaches the clinic. Producing the amount of cells needed will require a breakthrough in automated cell proliferation. Because of that, Takebe says, use in humans is at least a decade away.
Source: sciencemag
