Researchers fix mutation in reprogrammed stem cell, create functional liver

A group led by the Sanger Institute and the University of Cambridge, working with the Sangamo Biosciences, has shown that it's possible to fix mutations in reprogrammed cells. This work, which was published in Nature, takes two previous advances and combines them into one proof-of-concept.

Since 2007 stem cell scientists have been able to reprogram adult cells such as skin back into an embryonic-like state. These so-called iPS cells can then mature into any cell type in the body, much like embryonic stem cells.

Other groups have shown that it's possible to take adult stem cells such as those from the bone marrow, correct mutations, and create mutation-free cells that, at least in animal models, can fix diseases. That's the idea behind CIRM's two HIV/AIDS disease team awards (described here and here) and a sickle cell disease team. In fact, one of the HIV/AIDS disease teams is also working with technology developed by Sangamo to fix the mutations.

In the work reported in Nature, the team created iPS cells from a person with a genetic liver disease, fixed the mutation, then matured the iPS cells into functional liver cells. A Reuters story quotes Allan Bradley, director of the Sanger Institute:

"These are early steps, but if this technology can be taken into treatment, it will offer great possible benefits for patients," he added.

Reuters quoted David Lomas, who was part of the team from Cambridge, saying that the liver cells survived when transplanted into mice.

The researchers said it could be another five to 10 years before full clinical trials of the technique could be run using patients with liver disease. But if they succeed, liver transplants -- costly and complicated procedures where patients need a lifetime of drugs to ensure the new organ is not rejected -- could become a thing of the past.

"If we can use a patient's own skins cells to produce liver cells that we can put back into the patient, we may prevent the future need for transplantation," said Lomas.

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Miniature liver grown from stem cells

Researchers from Wake Forest University Baptist Medical Center have created a tiny, functional liver grown from stem cells. It's not big enough to process a half-time beer (Go Giants!), or much of anything else, but it's an interesting start.

The researchers presented their laboratory-grown liver, which is about the size of a walnut, at a meeting of the American Association for the Study of Liver Diseases.

Growing fully formed organs out of stem cells is thought to be a distant goal of stem cell research. That's because of the complexity of organs. Of the possible stem cell therapies that are expected to reach clinical trial, most involve transplanting a single cell type -- retinal cells for macular degeneration, nerve support cells for spinal cord injury, or insulin-producing cells for diabetes. Whole organs contain a complicated network of cell types that all have to work together in order for an organ to function.

The Wake Forest group took an existing liver and stripped it of all the liver cells, leaving behind the support structures like connective tissue and blood vessels. Onto that they placed liver stem cells, which then grew in a bioreactor to create a tiny new liver.

The BBC quotes Shay Stoker, who led the research, saying there's a long way to go before this tiny proof-of-principle is ready to replace organ donations:

"Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, we must determine whether these organs are safe to use."

That's many years of laborious time in the lab condensed into a single sentence. Scaling the liver up and proving its safety will be significant hurdles. Still, it's exciting to see these first steps toward what might one day be an alternative for thousands of people currently waiting on donated organs. 

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