Donor organs created by dissolving and rebuilding pig livers

We may one day be able to grow transplant organs on demand

Original source: New Scientist

A method that uses pig organs as scaffolding for creating new livers suggests we may one day be able to grow transplant organs on demand.

In an effort to tackle lengthy waiting lists for organ transplants, researchers have been trying several approaches for making replacement organs. One is to grow organs from stem cells. Another is to genetically alter pigs so the cells of their organs are more human-like, and less likely to be attacked by a recipient’s immune system.

Now an in-between method is taking off. It starts with an organ from an ordinary pig, but involves dissolving the cells to leave a protein scaffold in the original shape of the organ. This is then reinfused with human cells.

Until now, this technique – dubbed “decel/recel” – has been mainly investigated for small or thin structures such as layers of skin because it is hard to dissolve the inside of a large organ. But US firm Miromatrix announced in October that it has successfully created livers this way.

So far, the team has only created whole livers with pig cells rather than human cells. But this first step means the livers can be tested as transplant organs in pigs without the risk of them being rejected by the animals’ immune systems.

The whole livers were decellularised by pumping detergent through their blood vessels, so it reached everywhere. This removed every living cell, leaving behind only the structural proteins that held the organ in shape. With a pig liver, this process takes 24 hours.

The liver scaffold is then reinfused with the three main types of cell within a liver: liver, blood vessel wall and bile duct cells. These automatically home in on their right places within the scaffold, says Jeff Ross of Miromatrix. “It takes tissue engineering from a single layer to whole organs,” he says.

Ross and his colleagues have begun to try this with human cells. In a first step, the team pumped cells from human umbilical cords into the protein scaffolding, remaking the blood vessels of the liver. When these were implanted into pigs, the vessels survived and allowed blood to flow throughout the scaffold. These results were presented at a meeting of the American Association for the Study of Liver Diseases in Washington DC last month.

Ross says his team is now working on reinfusing liver scaffolds with human liver and bile duct cells, and plans to implant these into pigs by the end of 2017. The hope is to have livers made entirely from human cells that could be transplanted into people within three years. For this, the team will use liver cells from donated organs that are not in good enough shape to transplant into a patient.

But the real test will be to see how well the livers work, says Laura Niklason of Yale University. “The decellularisation and repopulation is not the tricky part – the tricky part is getting all the cells you put back in to behave properly.”

The experimental organ transplant field is under the spotlight after recent setbacks, including a scandal over trachea replacements at the Karolinska Institute in Stockholm, Sweden. Surgeon Paolo Macchiarini was found to have put them into patients without enough safety testing. In several of the procedures the patient later died or their trachea failed.