These liver buds were grown from iPS cells, a type of stem cell that can provide a perfect genetic match to anyone. The buds grew into functional livers after being transplanted into mice. (Takanori Takebe)
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Scientists trying to use stem cells to grow organs in the lab have been going about it the wrong way, Japanese researchers say. Instead of trying to make a fully functional organ to transplant into a patient, they should create an immature version and let it grow inside the patient’s body.
The researchers, from Yokohama City University, showed that their approach can make a human liver that performs essential liver tasks when placed inside a mouse. They described their experiments in a study published Wednesday by the journal Nature.
The Japanese team started with induced pluripotent stem cells, or iPS cells, which are capable of growing into any type of cell in the body. These stem cells are made by rewinding adult cells to an immature state; that means they can be used to make organs that are a perfect genetic match to anyone -- including a person who needs a liver transplant.
The researchers set as their goal the creation of a “three-dimensional liver bud.” Under normal circumstances, liver buds are made inside 3- or 4-week-old embryos and grow into mature livers as the embryo develops.
By placing the iPS cells into a lab dish with a carefully chosen combination of cells -- including some from a human umbilical vein -- the researchers were able to prompt them to grow into liver buds in about 48 hours. Tests revealed the experimental buds were expressing the same types of genes as a real liver bud.
That was about as far as the livers would go in the lab. What they needed next was a body -- a sophisticated biological environment that would send out just the right mix of signals to get the liver to grow. Transplanting the liver buds into humans was not an option for something so experimental, so the researchers put the buds into mice.
It took another two days for the buds to grow blood vessels and connect to the circulatory system. The vessel network looked the same as the ones around adult livers, according to the study.
After about 10 days, the transplanted liver buds began producing an essential protein called albumin. As more time passed, the buds grew into organs that resembled mature livers and expressed the same genes.
In a test of liver function, the researchers gave the mice two drugs to see how they would be metabolized by the animals. The result was “similar to that of a human adult liver” and different from the iPS cells the researchers started with, they reported. The authors were particularly excited by this finding, because it suggested the livers could be used to test drugs in humans without having to put any actual people -- or their livers -- at risk.
“We successfully generated ... functional human liver,” the Japanese team wrote. While emphasizing that they still have a long way to go, they said their approach can help address the “critical shortage of donor organs for treating end-stage organ failure.”
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