By Alice Klein
Lei Dong, Nanjing University
Repurposing the spleens of mice helps them to survive liver damage. If the approach works in people, it could offer an alternative to liver transplants.
At the moment, people who need new livers often have to wait a long time for a donor organ to become available. Scientists have tried engineering livers in the lab, but have found it too difficult to recreate their intricate blood vessel networks.
Lei Dong at Nanjing University in China and his colleagues wondered if, instead, they could transform an organ like the spleen – one that we can survive without and that already has ready-made blood vessels – into a working liver.
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To do this, they injected the spleens of live mice with a biological substance to make them larger and stiffer and better able to support the growth of new tissue. Next, they transplanted liver cells into the remodelled spleens to see if the cells would integrate with the existing blood vessels and develop into liver tissue.
Over the next eight weeks, the liver cells successfully grew in the spleens and developed into liver-like organs, complete with bile ducts and other liver structures. The converted organs were also able to perform essential liver functions such as drug metabolism.
Lei Dong/Nanjing University
Dong’s team then removed 90 per cent of the livers in the mice to see if their new spleen-based livers could take over. All the mice with spleen-based livers survived, whereas other mice died within two days of having liver tissue removed. “Our results suggest that we have transformed the spleen into an organ that functions as a liver,” the researchers write.
Could it work in people?
In humans, the spleen isn’t an essential organ, and people can have their spleens removed for medical reasons. Dong and his colleagues suggest that repurposing people’s spleens to act like livers could help them to overcome liver disease without causing other complications.
However, spleen-based livers couldn’t perform all the functions of real livers because they are hooked up differently to the circulation, says Geoff McCaughan at the University of Sydney, Australia. For example, one job of the liver is to detoxify blood coming from the portal vein, but the spleen has no direct access to this vein, he says.
Another issue is that people with serious liver disease often also have damaged spleens, which may make it difficult to transform them into liver-like organs, says Eric Lagasse at the University of Pittsburgh, Pennsylvania. “It will take a while to see if such an approach works in humans or is even feasible,” he says.
If the approach doesn’t work, one solution may be to grow liver-like organs in the lymph nodes instead, which are well-suited to nurturing the growth of new tissue and are less prone to damage than the spleen, says Lagasse.
In fact, Lagasse and his colleagues have already shown that liver-like organs can be grown in the lymph nodes of mice with severe liver disease. They are hoping to trial the approach in people “very soon”, he says. The idea of turning one organ into another may sound far-fetched at the moment, but it “may be not such a crazy idea”, he says.
Journal reference: Science Advances, DOI: 10.1126/sciadv.aaz9974
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