A lab-grown oesophagus has been successfully transplanted into pigs for the first time, restoring normal swallowing in the animals.
The UK-based study showed that grafts (sections of lab-grown tissues) built from the cells of the recipient pigs could progressively develop the structures required for a working oesophagus, without the need for anti-rejection medication. The approach, published in Nature Biotechnology, was designed to mirror the clinical pathway for treating children with long-gap oesophageal atresia (LGOA), a condition in which babies are born with a gap between the upper and lower parts of the oesophagus.
Study lead Professor Paolo De Coppi, a consultant paediatric surgeon at Great Ormond Street Hospital and head of stem cells and regenerative medicine at University College London Institute of Child Health explained that '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 process took around eight weeks in total. It first involved stripping donor pig's oesophagi of their cells to create structural scaffolds. These structures were then injected with stem cells from each intended recipient pigs, and placed in a bioreactor for a week – a controlled environment that keeps cells alive and primes them for implantation. Biodegradable stents were inserted after implantation to hold the graft open while it healed.
Out of the eight pigs that received the transplant, all developed the muscle contractions needed to push food toward the stomach. Five survived to the planned six-month endpoint, by which point the animals could swallow and their grafts had developed functional muscle, nerves, and blood vessels.
LGOA affects around 18 newborns in the UK each year. Current treatments, such as connecting the stomach directly to the throat, or transplanting part of the colon, are invasive and can carry significant long-term complications. The researchers' goal is to create personalised grafts from donor pig scaffolds with a child's own stem cells injected, matched to the patient in size and designed to integrate with the body as the child grows.
However, Professor Dusko Ilic, professor of stem cell sciences at King's College London – who was not involved in the research – said: 'The study represents a significant advance in engineering functional replacements for complex hollow organs… However, the suggestion that this approach offers a solution for children born without an oesophagus is premature.' In his view, longer studies are needed to show whether the graft truly behaves as a dynamically growing tissue, noting that so far 'there is no evidence that the construct can accommodate somatic growth.'
The team plans to scale up and standardise production of lab-grown oesophageal grafts, conduct further safety and functional testing, and prepare for first-in-human trials, which they hope to begin within five years.
Sources and References
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Engineered tissue offers hope for babies born with missing food pipe section
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Functional integration of an autologous engineered esophagus in a large-animal model
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Lab-grown oesophagus restores pigs' ability to swallow
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Lab-grown food pipe offers new hope for young patients
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First lab-grown oesophagus successfully implanted in pigs
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Lab-grown esophagus offers hope for children with long-gap esophageal atresia
