TOKYO -- A Japanese group has generated functional human livers by creating liver precursor cells in the laboratory and then transplanting them into mice to complete the developmental process. Their ultimate goal is to transplant the precursor cells into humans and let them develop into replacements for diseased or damaged organs.
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 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 four to five-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 these tiny organs produced proteins typically made by human livers, and they properly processed certain drugs that mouse livers cannot handle. This "proof of concept demonstration" provides a promising new approach to regenerative medicine, the team writes in a paper published online by Nature recently.