Lab-grown organoids can help repair damaged livers, University of Cambridge research shows
University of Cambridge scientists have shown that bile duct organoids they have grown in the lab can be used to repair damaged livers.
It is the first time the technique has been used on human organs.
With further work on the safety on the concept, the research on the ‘mini-organs’ could lead to cell therapies that will help repair a patient’s own liver, or to repair damaged organ donor livers so they can be used for transplantation.
The team used a ‘perfusion system’ that is capable of maintaining donated organs outside the body to demonstrate that it is possible to transplant biliary cells grown in the lab, known as cholangiocytes, into damaged human livers to repair them.
They repaired livers deemed unsuitable for transplantation due to damage in the bile ducts, which act as the liver’s waste disposal system.
Malfunctioning bile ducts are behind a third of adult and 70 per cent of children’s liver transplantations, and there are no alternative treatments.
Dr Fotios Sampaziotis, from the Wellcome-MRC Cambridge Stem Cell Institute, said: “Given the chronic shortage of donor organs, it’s important to look at ways of repairing damaged organs, or even provide alternatives to organ transplantation.
“We’ve been using organoids for several years now to understand biology and disease or their regeneration capacity in small animals, but we have always hoped to be able to use them to repair human damaged tissue. Ours is the first study to show, in principle, that this should be possible.”
Using single-cell RNA sequencing and organoid culture techniques, the researchers found that biliary cells from the gallbladder could be converted to the cells of the bile ducts usually destroyed in disease (intrahepatic ducts) and vice versa, using a component of bile known as bile acid. It means a patient’s own cells from areas from disease could be used to repair destroyed ducts.
They tested the theory by growing gallbladder cells as organoids – 3D clusters of cells with the same tissue architecture, function and genetic activity as the original organ. They grafted these gallbladder organoids into mice and found that they repaired damaged ducts, opening up potential regenerative medicine applications. They also injected the gallbladder organoids into a human liver – using the perfusion system in use at Addenbrooke’s – and showed for the first time that the transplanted organoids repaired the organ’s ducts and restored their function.
Professor Ludovic Vallier, from the Wellcome-MRC Cambridge Stem Cell Institute, joint senior author, said: “This is the first time that we’ve been able to show that a human liver can be enhanced or repaired using cells grown in the lab. We have further work to do to test the safety and viability of this approach, but hope we will be able to transfer this into the clinic in the coming years.”
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