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Lab-grown organoids repair damaged human livers

Friday February 19th 2021

Laboratory-grown organoids have been used for the first time to repair damaged human livers, potentially paving the way for cell therapies to treat liver disease, British researchers have announced.

Writing in the February edition of Science, scientists at the University of Cambridge, UK, say their new approach takes advantage of a recently introduced “perfusion system”, which can be used to maintain donated organs outside the body.

Using this technology, they showed it is possible to transplant lab-grown cholangiocytes into damaged human livers to repair them.

As proof-of-principle, they repaired livers deemed unsuitable for transplantation due to bile duct damage and say their approach could be applied to multiple organs and diseases to accelerate the clinical application of cell-based therapy.

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 the techniques of single-cell RNA sequencing and organoid culture, the researchers discovered that although duct cells differ, biliary cells from the gallbladder, which is usually spared by the disease, could be converted to the cells of the intrahepatic ducts, and vice versa, using bile acid.

This means the patient’s own cells from disease-spared areas could be used to repair destroyed ducts.

To test the hypothesis, the researchers grew gallbladder cells as organoids in the lab, which were grafted into mice. It was found they could repair damaged ducts, opening up avenues for regenerative medicine applications in the context of diseases affecting the biliary system.

The team went on to use the technique on human donor livers and injected the gallbladder organoids into the human liver and showed for the first time that the transplanted organoids repaired the organ’s ducts and restored their function.

Joint senior author Professor Ludovic Vallier, from the Wellcome-MRC Cambridge Stem Cell Institute, 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.”

Mr Kourosh Saeb-Parsy, from the Department of Surgery at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, joint senior author, added: “This is an important step towards allowing us to use organs previously deemed unsuitable for transplantation. In future, it could help reduce the pressure on the transplant waiting list.”

Sampaziotis F et al. Cholangiocyte organoids can repair bile ducts after transplantation in human liver. Science 18 February 2021

Tags: Internal Medicine | UK News

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