Researchers have demonstrated that a bioengineered esophagus can successfully replace the organ in a large animal model, restoring function without the need for immunosuppressant drugs. This breakthrough, detailed in a study published in Nature Biotechnology, offers potential hope for children born with severe esophageal atresia.
A laboratory-grown esophagus, capable of integrating into the body and functioning like a natural one, may soon become a clinical reality. This finding emerges from a study conducted by researchers at Great Ormond Street Hospital and University College London (with collaboration from Bambino Gesù Pediatric Hospital, University of Tor Vergata, and Politecnico di Milano), published in Nature Biotechnology, led by Professor Paolo De Coppi. For the first time, a bioengineered esophagus has successfully replaced an entire segment of the organ in a large animal model, allowing for normal swallowing and eliminating the need for immunosuppressant medications. This represents a significant step toward personalized therapies based on regenerative medicine.
Congenital Malformations and Current Treatment Limitations
The esophagus is essential for nutrition, and growth. In cases of esophageal atresia with a “Long gap” (LGEA) – a rare but serious condition – the tube connecting the mouth and stomach is interrupted, and the two segments are too far apart to be surgically connected immediately after birth.
These infants cannot survive without complex interventions: they often require a feeding tube and multiple invasive surgeries. These procedures can lead to significant short- and long-term complications, including respiratory and gastrointestinal problems, and an uncertain long-term cancer risk. Although many children achieve good outcomes, better options with fewer complications are needed.
Esophageal Malformations in the UK and Italy
Great Ormond Street Hospital (GOSH) is a leading center for treating these malformations: approximately 180 children are born with esophageal atresia in the United Kingdom each year, with 10% presenting with the “Long gap” form. In Italy, 150 children are born with the condition annually (10% with “Long gap”), and Bambino Gesù Hospital is among the leading European referral centers.
Current surgical options are complex and invasive. One approach involves moving the stomach or intestine to bridge the gap, but these are major surgeries with significant short- and long-term complications. The findings from this study offer a potential path toward less invasive and more effective treatments for this challenging condition.
How a Bioengineered Esophagus is Created
The new results achieved in London build on the field of regenerative medicine, which has seen renewed momentum in recent years. The technique involves starting with an esophagus from a pig (“donor”) – which is particularly similar to a human esophagus – to serve as a “scaffold” for the new organ. Through a decellularization process, all the pig cells are carefully removed from the donor tissue, leaving the underlying support structure intact.
Subsequently, the scaffold is repopulated with muscle cells from a pig “recipient,” obtained from a small biopsy. These cells are multiplied in the laboratory and then injected directly into the scaffold. The graft is then placed in a bioreactor, a special container that pumps vital fluids through the tissue for one week. During this time, the cells settle in, spread out, and adapt to their new “home.” The entire process takes two months to complete, a timeframe consistent with current standard treatments for LGEA.
Study Results: A Functional, Growing Organ
The results obtained in the animal models are particularly promising. All eight animals survived the first 30 critical days after the transplant. After six months, the grafts had developed functional muscles, nerves, and blood vessels, allowing the transplanted esophagus to contract and push food like a natural organ. The animals were able to feed normally and grow healthily. Some developed constrictions ( stenoses), which were successfully managed with endoscopy, as in human clinical practice.
For the first time, the team similarly mapped gene expression in the implanted tissue, demonstrating that the activated genes were consistent with those of a natural esophagus. Progressive regeneration of normal structures, including a barrier layer, muscles, nerves, and blood vessels, was observed. The bioengineered esophagus proved capable of contracting and generating sufficient movements and pressures to allow for normal swallowing.
Professor Paolo De Coppi, who led the study, explains: “The esophagus is a very complex organ and cannot be transplanted in the traditional way. To develop alternatives, it is essential to use animal models similar to humans. With these results, we hope to be able to offer a bioengineered alternative to children who need it within five years.”
Researcher Marco Pellegrini added: “This technology allows us to build an esophagus using the child’s cells, taken during a procedure already planned. Being the patient’s own tissue, it can grow with the patient without the risk of rejection and without immunosuppression.”
First author of the study, Natalie Durkin, concluded: “After implantation, our grafts grew, matured, and began to function like natural tissue. Each step represents a crucial step toward clinical application.”
Next Steps Toward Human Trials
The next step will be to optimize tissue production, increase its length, and standardize the process, as well as continue safety testing. The goal is to begin clinical trials in humans within five years.
Professor De Coppi believes this technology could represent a new frontier in regenerative medicine, comparable to the introduction of animal-derived heart valves: “For over 50 years, porcine heart valves have been used to save lives. More recently, xenotransplantation has been explored as a solution to the organ shortage. Our function demonstrates that porcine tissue, once deprived of cells, can become a scaffold for creating compatible tissues.”
“From a conceptual point of view, this work is fundamental because it reminds us that there is a sector that is progressing: cellular, tissue, and solid organ bioengineering,” comments Professor Giuseppe Orlando, president of the Cell Transplant and Regenerative Medicine Society (CTRMS) and the advisory committee for regenerative medicine of the American Society of Transplantation (AST). “Although a complex organ like a kidney or heart has not yet been implanted in a patient, the biotechnologies currently available allow the production of less complex organs such as the bladder, urethra, and upper airways, which have already been implanted in patients for many years. And it is worth remembering that the Italian school of bioengineering founded by Ranieri Cancedda, has conducted pioneering studies in this field, carried out by scientists of the caliber of Michele De Luca, Graziella Pellegrini and Ivan Martin.”
“In the not-too-distant future,” concludes Orlando, who is also a professor of Surgery and regenerative medicine at Wake Forest University School of Medicine (USA), “transplantation will be very different from what it is today. When xenotransplantation and bioengineered organs become a remarkable clinical reality, there will be no need to take organs from human donors, whether deceased or living. There will be banks of cells, tissues or organs, which will have been engineered (i.e., produced) from pigs or human stem cells, which will then be cryopreserved, to be offered to patients when requested by the attending physician.”
