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Liver Buds Show Promise, but Growing New Organs Is Still a Long Way Off

Watch this time lapse video showing how three types of stem cells organized into a three dimensional liver bud over 72 hours. Video by Takanori Takebe

When stem cell biologist Takanori Takebe at Japan’s Yokohama City University first saw his results in a petri dish, the feeling was hard to describe.

“I think ‘gobsmacked’ is the closest word in English,” said translator Matthew Salter from the journal Nature’s Tokyo office, during a press briefing on Tuesday.

Takebe and his team had mixed three cell types: adult stem cells engineered for a human liver, adult bone marrow stem cells and stem cells from a human umbilical cord. The cells self-organized into a liver bud — a tiny, three dimensional, functioning piece of human liver, complete with a vascular system to deliver blood to the organ. When Takebe transplanted the liver bud into a mouse, it thrived, functioning like a human liver.

It also helped bring the mouse back from liver failure, an important step in the team’s conclusion that the liver bud was functioning, Takebe told the press.

Creating fully functioning organs for transplant has been a goal of stem cell research since work on embryonic stem cells began in the 1980s. As of today there are 118,647 people in the United States on the waiting list for new organs, according to the US Department of Health and Human Services. Takebe’s hope is transplanting hundreds of these liver buds could restore up 30 percent of a patient’s liver function. This technique could work for other organs like the pancreas, Takebe said in his paper, and perhaps lead to creating a full liver.

The group’s findings are published in this week’s issue of the journal Nature.

Dr. Timothy Nelson, director of the Regenerative Medicine Consultation Service at the Mayo Clinic, says when studies like this come out, he gets lots of questions from families, hopeful that this means a new treatment for their sick loved ones. Not yet, he always cautions them. It can take 10 years for the proof-of-concept study in a lab to become a clinical trial — and that’s optimistic, he said.

“I spend a lot of time talking to patients about the hope and hype of stem cell biology,” he said. “I try to leave them with the message that let’s be hopeful, but as of today it’s not possible to bring that to your patient.”

There are stem cell therapies currently in the trial phase in the U.S., Dr. Nelson tells his patients. But only one stem cell product — Hemacord — has been approved by the FDA, and another nine or ten stem cell therapies have been approved, mostly to treat blood diseases like leukemia and healing skin tissue.

It’s another light at the end of the tunnel, said Dr. Mahendra Rao, director of National Institute of Health’s Center for Regenerative Medicine. As little as two years ago, scientists had shown you could grow three dimensional organs in the lab using stem cells, he said, including an eye. He says that while he doesn’t consider Takebe’s research an earth-shaking discovery in that regard, it’s an exciting step forward in this field of research.

“The holy grail [of regenerative medicine] has been not only being able to do cell transplants, but having three dimensional organs for transplant,” he said. “But a fundamental limitation has been the blood supply.”

It’s one reason so many cell transplants have failed in the past, said Dr. Joseph Wu, who is a professor of medicine and radiology and director of the Stanford Cardiovascular Institute at Stanford University School of Medicine. Without a ready supply of blood, the new cells die, he said. When it comes to growing a new organ, or even new tissue, there are several challenges the public needs to be aware of.

“People think I can take stem cells and inject them into a patient and they work like magic, and they keep regenerating,” Wu said. “Most of these stem cells die.”

And to create a new organ, the stem cells need specific cues and direction, especially to form the complex shapes, flexibility and structure of an active organ like the heart, he said.

“Hurdles are everywhere. Why do the cells die? How do you make sure these manipulated cells are not rejected by the body’s immune system? How do you make sure these differentiated cells are not tumorigenic?” Wu asked.

Even when those biological hurdles are cleared, biotechnology needs to go through rigorous approval for use in humans, Dr. Nelson said, which takes time and money. Biotechnology could take a cue from other industry sectors like pharmaceuticals, and reduce that ten year waiting time between the lab and the clinic, he said. But this field is still moving forward much more rapidly than anyone anticipated, even five years ago, Nelson added.

“What we thought to be impossible when I was in training will be the expected norm in coming years,” he said. “So I wouldn’t be pessimistic.”

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