Scientists Engineer Human Livers


Many people need new organs, but the numbers that are available don’t begin to meet the demand. At Wake Forest University an effort to solve that problem – at least for livers – is bearing fruit.

The team of researchers, led by Shay Stoker, a professor of regenerative medicine, and Pedro Batista, a doctor of pharmacy, has used human liver cells to successfully grow a small version of the organ.The liver is just large enough to be transplanted into a rat. That’s the next step, says Batista – to see if the new liver takes over the function of one that isn’t functioning.

To build a liver, the researchers took an animal liver and removed the liver cells with a mild detergent, leaving only the skeleton. The liver skeleton is a scaffolding of tissue, rather than bone, but it still offers a way for the cells to organize themselves. They then placed liver progenitor cells and cells that line blood vessels. When the cells were provided with nutrients, they grew into a small liver.

Batista says the livers will be implanted in rats that are given cirrhosis.  In humans cirrhosis is often caused by alcoholism. (In rats, it is induced by other methods). The rodent experiments will also help show whether the new livers are safe to use.

If successful, the work will show that it is possible to engineer a human liver from relatively few cells, which could be harvested from the patient who needs one before being grown.

There are many billions of cells in a liver, and even in rat-sized livers there are hundreds of millions. Batista says his team’s technique can grow a liver from only a few million cells, or about four milliliters worth.

To make a fully functional human liver they would need to regenerate about a pound of liver tissue. A full liver weighs about three pounds, but even a portion of a liver can provide enough function while it regenerates naturally. The engineered livers are a long way from that – right now they weigh about 0.2 ounces.

One thing that makes livers interesting, Batista says, is that more than any other organ they can regenerate. That makes the regenerative medicine simpler. But livers are not simple organs – there are no less than four different vascular systems in them.

The new livers do have limitations. They don’t have a system of bile ducts, only the cells that process the toxins. As time goes on they could get better at regenerating those systems, Batista says.

Ultimately, regenerating livers could be used to treat liver disease and supplement -or even replace — transplants.

“There are 16,000 people waiting for a liver,” Batista said. “Maybe 5,000 will get one, and 10-20% of those waiting will die.”

Batista says his own interest in livers comes from being a pharmacist. In drug development and use, the liver is one of the most important organs as it processes the toxins and drugs people ingest. “We’re always interested in livers as pharmacists,” he said.

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