Lab-grown esophagus offers hope for children with long-gap esophageal atresia
Lab-grown organs offer personalized, immunosuppression-free solutions for life-threatening conditions.
Scientists from Great Ormond Street Hospital (GOSH) and University College London (UCL) have developed the first lab-grown esophagus capable of safely replacing a full section of the organ and restoring normal function, including swallowing, in a porcine model without the need for immunosuppression. This breakthrough represents a significant step toward personalized regenerative treatments for children with life-threatening esophageal conditions and has potential applications in other disease areas. While previous studies demonstrated parts of this technology, this is the first time the entire process has been successfully completed.
Children with long-gap esophageal atresia (LGOA) are born with a disrupted esophagus, leaving a large gap between the upper and lower segments. Approximately 180 babies are born with esophageal atresia (OA) in the UK each year, 10% of whom have LGOA. These children cannot survive without surgery, but the gap is often too large to close immediately after birth. As a result, they typically require a feeding tube for nutrition while awaiting treatment. Current surgical options are complex and invasive, and while many children achieve good outcomes, there is a pressing need for safer, less invasive alternatives.
The study demonstrated that a donor pig esophagus can be decellularized, repopulated with the recipient pig’s own cells, and implanted in a growing animal model to restore function without immunosuppression. The eight recipient pigs recovered well, developing functional swallowing muscles and achieving full integration of the engineered tissue within three months. Immunosuppression was unnecessary because the implant was created using the recipient’s cells, allowing the tissue to grow with the animal.
The process begins with creating a scaffold from a donor pig’s esophagus, which closely resembles a human esophagus. Through decellularization, the donor tissue is stripped of all pig cells while preserving the structural framework. The scaffold is then repopulated with muscle cells from the recipient pig, obtained via a small biopsy. These cells are multiplied in the lab and injected into the scaffold, which is placed in a bioreactor for one week to promote cell growth and adaptation. The entire process takes two months, aligning with current treatment timelines for LGOA.
The results in pigs were highly promising. All eight animals survived the critical first 30 days post-transplant, and by six months, the grafts had developed functional muscle, nerves and blood vessels. The engineered esophagus contracted and moved food effectively, allowing the animals to eat normally and grow at a healthy rate. While some animals developed strictures (narrowing of the esophagus), these were successfully treated with endoscopy, similar to standard human clinical practice.
For the first time, researchers used spatial transcriptomics to map gene activity in the implanted tissue, confirming that the gene expression matched that of natural esophageal tissue. Over time, the engineered esophagus regenerated key structures, including a barrier layer, muscle, nerves, and blood vessels, enabling normal swallowing function.
If adapted for human use, this technology could provide ready-to-use scaffolds derived from donor pigs, personalized for newborns or children of different sizes and ages. Biopsy cells could be collected when a feeding tube is placed and incorporated into the scaffold, creating a custom graft that grows with the child and eliminates the need for immunosuppressants.
The team is now refining the process to generate longer grafts, standardize manufacturing and reduce manual steps, and carry out further safety testing. Further studies will focus on tracking the cells on the tissue, optimizing blood flow and preparing the therapy for first-in-human trials. The team hope to be able to offer this as a research trial in the next 5 years.
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