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Scientists at Massachusetts General Hospital in Boston have taken the first steps toward building functional, transplantable livers. In a study in rats, published online today by Nature Medicine, the researchers took donor livers, gently stripped them of their cells while leaving other material intact, and then used the remaining structure as a scaffold on which to grow healthy liver cells. The result was a nearly complete organ that was transplanted into the rats and remained functional for up to eight hours.

Liver disease is the 12th-largest cause of death in the United States, while heart and kidney disease rank even higher. The symptoms of organ failure can be treated to some extent, but the only cure is transplantation, and there just aren’t enough healthy donor organs to go around. For decades, researchers have been working to build replacements. But organs are complex systems, with a cell density and blood-vessel system that are difficult to replicate.

The new technique, which was first demonstrated in hearts two years ago, takes advantage of an organ’s preexisting structure in all its intricacy, and provides a use for unhealthy organs that could not otherwise be used. “We try to resuscitate organs that would be discarded and do things to make them transplantable,” says Basak Uygun, the paper’s first author and a researcher at the Center for Engineering in Medicine at MGH.

Other approaches for organ regeneration have varied widely, from creating lab-made scaffolds to using ink-jet printers to create three-dimensional tissue. But all of these methods try to mimic what the body has already successfully created. The “decellularization” technique capitalizes on that, removing what’s broken and replacing it with healthy new cells. “What we’ve done is basically take the shortcut,” says Korkut Uygun, the researcher at the Center for Engineering in Medicine who led the work.

“This leapfrogs other approaches,” says Stephen Badylak, a specialist in tissue engineering at the University of Pittsburgh’s McGowan Center for Regenerative Medicine. “The beauty of this approach is that it doesn’t try to synthesize anything. It tries to isolate Mother Nature’s three-dimensional scaffold and take advantage of that. If this can be translated to the clinic–and we’re still a ways away from that–it’s a tremendous advance.”

Uygun and her colleagues started with livers from rat that had died from oxygen deprivation. They decellularized the livers with a detergent, which killed off the remaining cells and removed their debris. What remained was a delicate scaffold of proteins and sugars and other extracellular structures, including blood vessel architecture–the most complex aspect of the liver, the hardest to duplicate, and the one most necessary for the survival of the new cells. The scientists seeded the scaffold with liver cells isolated from healthy rat livers, as well as endothelial cells to line the blood vessels, and the result remained functional in culture for 10 days.

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Credits: Brittany Sauser
Video by Brittany Sauser

Tagged: Biomedicine, regenerative medicine, organ transplants, liver cells, MGH

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