A Great Ormond Street Hospital study means children born with missing part of oesophagus could have a new food pipe engineered in a lab using tissue from a pig
Children born with a missing part of their oesophagus could have a new food pipe engineered in a lab using tissue from a pig.
Around 180 children are born in the UK each year with a missing section and some require a food pipe fitted as well as facing a risk of complications. The first lab-grown organ using the oesophagus of a pig engineered together with the recipient’s own cells has been shown to work and could be offered to human patients in five years.
The breakthrough offers hope to families with children born with the condition and one parent whose two-year-old son has spent half his life in hospital said it would be “life-changing”.
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A two-month trial of saw pigs given a lab-grown oesophagus using a donor pig’s food pipe showed they were able to swallow and eat normally, and did not need drugs to stop their body rejecting the organ. Senior researcher Dr Marco Pellegrini, of Great Ormond Street Hospital and University College London, said “Our technology could allow us to build a child a new oesophagus, using their own cells, collected in a surgery they are having anyway, combined with a ready-prepared scaffold from pig tissue.
“Because the graft contains the child’s own muscle progenitor cells, it would be recognised as their own tissue. This means it could grow with them over time, without the risk of rejection and without the need for long-term immunosuppression.”
A “scaffold” was created using a donor pig’s oesophagus, acting as a tube-shaped base for the new organ before being stripped of all pig cells. Scientists then took muscle cells from the recipient pig, which were multiplied in the lab before being injected directly into the scaffold.
The tube was placed in a special container that pumped growth fluids through the tissue for one week. All eight pigs survived the first 30 days after the transplant. After six months, five remained alive and the lab-grown scaffolds had developed functional nerves, blood vessels and muscle, allowing it to contract and move like an oesophagus. The animals could eat normally and grew at a healthy rate.
Oesophageal atresia (OA) affects about 180 births in the UK every year. Usually, surgery is performed on babies soon after birth to close the gap. In one in ten cases have long-gap oesophageal atresia (LGOA), which means the gap is too large to close immediately after birth. These babies typically require a feeding tube to get nutrients directly to the stomach for months before having surgery.
Experts said other options include an operation to bring the stomach into the chest, known as a gastric pull-up. But this can lead to further surgeries and complications such as reflux into the lungs which can cause lung disease in the long term. Two-year-old Casey McIntyre, from London, was born with 11cm of his food pipe missing. His mother, Silviya Lukanova, 38, said: “He’s had major operation after major operation as we simply couldn’t get the gap to close using his own tissue.
“After being referred to Gosh, we had the best option at the time – pulling up his stomach to close the gap but it’s been a long road and he still has a feeding tube while he develops his swallowing. The repeated surgeries have left him with some damage to his vocal cords so he’s developing his speech and noise-making to catch up. Once he’s eating enough through his mouth, we’ll be able to take his tube out.”
Casey’s father, Sean Mcintyre, 35, said: “Whatever the team did for him was really a miracle but the idea that there could be one operation early in your child’s life, that could transplant a working piece of oesophagus, and then we could move on would be life-changing.”
For the first time scientists were also able to map the genes in the implanted tissue. If adapted for humans, different sized scaffolds could be stored ready to be developed and personalised for newborns or children with LGOA. Biopsies could be taken from youngsters when having feeding tubes fitted.
Professor Paolo De Coppi, consultant paediatric surgeon at Gosh, said that pig heart valves have been used to extend and save the lives of patients for more than 50 years. He added: “I believe we are now standing at a similar new frontier. We designed the study to do exactly what can be done eventually in children.
“The oesophagus is a really complex organ, without a blood supply from its own vessels, so it cannot be transplanted in the way you might expect. To develop alternatives, it is essential to work with animal models that closely reflect human anatomy and function. The pig oesophagus closely resembles the human one.
“With the success of this research, we hope that we can be successfully offering an engineered tissue alternative to children who desperately need it, within five years.”
