Great Ormond Street Hospital Creates World's First Lab-Grown Oesophagus That Works in Living Animals, Paving Way for Human Trials

Scientists at Great Ormond Street Hospital and University College London have created the world's first laboratory-grown oesophagus — the muscular tube that carries food from the throat to the stomach — that successfully replaced the organ and restored normal swallowing function in living animals without the need for immunosuppressive drugs. The result, published March 20 in the journal Nature Biotechnology, was described by independent experts as a genuine landmark in regenerative medicine, offering the first realistic path toward a surgical solution for thousands of children born each year with a congenital condition that leaves them unable to swallow normally.

The research is the culmination of more than a decade of work by a team led by Professor Paolo De Coppi at GOSH's Stem Cells and Regenerative Medicine Section and Professor Martin Birchall at UCL's Institute of Laryngology and Otology. The technique begins with a donor pig oesophagus, which is chemically stripped of all cells through a process called decellularisation, leaving behind a ghostly white protein scaffold that preserves the organ's three-dimensional architecture — its shape, stiffness, and surface chemistry — without retaining any cellular material that might trigger immune rejection. That scaffold is then seeded with the recipient animal's own muscle stem cells, placed in a bioreactor that mimics the mechanical stresses and biochemical environment of a developing food pipe, and cultured for approximately two months before implantation.

Eight recipient pigs received the engineered oesophagi, each replacing a section of their natural food pipe. All eight animals survived the critical first 30 postoperative days. By six months, detailed histological analysis showed the grafts had successfully recruited functional muscle fibers, developed an enteric nerve network capable of generating the coordinated peristaltic contractions needed for swallowing, and established a robust blood supply. Most critically, the animals showed normal swallowing function and maintained healthy weight gain throughout the observation period — they were eating normally. Because the grafts were populated exclusively with the recipient's own cells, none of the animals required immunosuppressive drugs at any point. This is the feature that experts immediately seized on as transformative: in conventional organ transplantation, recipients must take immunosuppressants for life, and these drugs carry serious risks including increased susceptibility to infections and certain cancers, especially dangerous in young children.

The target patient population is children born with long-gap oesophageal atresia, a congenital defect in which the oesophagus fails to form fully, leaving a gap that makes feeding impossible without surgical intervention. Approximately 18 children are born with the condition in the United Kingdom each year, and several hundred more in the United States. Current treatments — which typically involve multiple complex operations over years to stretch or reconstruct the existing oesophagus, or to replace it with a repurposed segment of stomach or colon — are painful, carry significant complication risks, and frequently do not restore normal function. Children with the condition often describe years of hospitalizations, feeding tubes, and anxiety about nutrition. A tissue-engineered replacement grown from the patient's own cells could eliminate the immunosuppression problem entirely and be tailored precisely to each child's anatomy.

Professor De Coppi said the results exceeded what the team had projected at the outset of the animal trials. 'What we showed is that the scaffold becomes a living organ,' he told colleagues at a presentation in London. 'It recruits muscle, it recruits nerves, it works. The next step is to confirm safety in a model physiologically closer to the human system.' Clinical trials in children are expected to begin within five years, pending regulatory review by the UK's Medicines and Healthcare products Regulatory Agency and completion of additional preclinical safety studies. UCL said it was already in discussions with MHRA to design a human trial protocol. For families of children born with oesophageal atresia, the research represents the first time a curative, immunosuppression-free surgical option has moved from theoretical possibility to demonstrated biological reality.