First lab-grown oesophagus offers hope to children born with rare condition

The first oesophagus to be engineered in a lab could allow children born with part of their food pipe missing to have a new organ grown for them using their own cells and pig tissue, scientists believe.

Babies born with long-gap oesophageal atresia (LGOA), a rare condition which causes the food pipe to be separated by a wide gap, cannot survive without surgery and face a higher risk of complications.

Experts who have been working on the technology for more than a decade are hopeful that engineered tissue treatments can be offered to these youngsters within five years.

One family whose two-year-old son has spent half his life in hospital with LGOA said it would be “life-changing”.

The pigs that received the lab-grown oesophagus for the research were able to swallow and eat normally, and did not need drugs to stop their body rejecting the organ.

The study was led by experts at Great Ormond Street Hospital (Gosh) and University College London (UCL), with the process taking about two months from start to finish.

First, 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.

Then, scientists 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, according to researchers.

Dr Marco Pellegrini, senior researcher at UCL Great Ormond Street Institute of Child Health (UCL GOS ICH), 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.”

For the first time, scientists were also able to map the genes in the implanted tissue.

They found the genes that were turned on in the new organ were in line with what would be expected in natural tissue.

Dr Natalie Durkin, paediatric surgical registrar and lead author of the study from Gosh and UCL GOS ICH, added: “After successful implantation, our grafts grew, matured and began to function like native tissue.

“Each one of these steps represents a key milestone in being able to deliver this as a viable treatment option for children in the near future.”

If adapted for humans, researchers suggest 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, they said.

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.

However, about 10% of cases have 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.

However, this can lead to further surgeries and complications such as reflux into the lungs which can cause lung disease in the long term.

Professor Paolo De Coppi, NIHR and Nuffield professor of paediatric surgery at UCL GOS ICH and consultant paediatric surgeon at Gosh, said: “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.

“In this respect, 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.”

Prof De Coppi said that pig heart valves have been used to extend and save the lives of patients for more than 50 years.

“I believe we are now standing at a similar new frontier in regenerative medicine,” he added.

“We designed the study to do exactly what can be done eventually in children.”

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 the memories of their son’s treatment “will never leave” the couple.

“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.”