GOSH team reveals the world’s first functional tissue engineered oesophagus

A pioneering new study from Great Ormond Street Hospital (GOSH) and The Francis Crick Institute has seen researchers grow the world’s first oesophagus engineered from stem cells and successfully transplanted them into mice, according to results published in the Nature Communications journal today (Tuesday 16 October 2018).

It is hoped this new research could pave the way for clinical trials of lab-grown food pipes for children with congenital and acquired gut conditions.

In the study, researchers used a rat oesophagus “scaffold” and human gut cells to grow engineered tubes of oesophagus. These were implanted into mice and within a week the engineered tissue developed its own blood supply, which is important for a healthy gut that can squeeze down food.

Children who could benefit in the future from further clinical trials include young patients like two-year-old Hudson who has oesophageal atresia, a rare congenital condition affecting nearly 250 in the UK each year. The condition results in an incomplete oesophagus, which ultimately impacts a baby’s ability to feed as well as their long-term health. His mum, Nicola, first became aware of the condition during a routine pregnancy screening, when a scan revealed that his abdomen was especially small compared with his identical twin, Hank.

Hudson was referred to GOSH where Consultant, Paolo De Coppi, recommended a gastric pull-up, lifting his stomach up towards the chest in order to connect the throat directly to the stomach. As a result of the procedure, Hudson can now enjoy some of the same foods as his twin, but needs continued feeding support.

Nicola said: “Hudson just wants to play and do the same things as his twin and other brother. Like most toddlers, he’s picky about what he eats and is wary of certain textures, which can be tricky when you’re trying to feed him a nutritious meal that meets all of his needs. There are things that we take for granted, which we don’t even think about doing, like breathing whilst eating. Hudson sometimes struggles to do both at the same time, so he has to eat with care. Explaining to any two-year-old why they have to sit and eat slowly is quite tricky, but his wellbeing and life depend on it.”

Around one in 3,000 babies (in the UK) are born with a life-changing defect of the gut. With one of the largest breadth of specialties under one roof, it is exceptionally placed to treat children with oesophageal atresia. The hospital’s pioneering research programme and state of the art stem-cell research facility at UCL Great Ormond Street Hospital Institute of Child Health (ICH) increases our capacity to find treatments and cures for complex childhood illnesses, benefitting families at GOSH and worldwide.

Speaking of the research Nicola added: “Having the gastric pull-up has helped my son thrive, but this latest research has the potential to change Hudson’s life and the life of other children with his condition. In a case like Hudson’s an entirely new, functioning foodpipe would without a doubt be a game changer, giving him a sense of normalcy, so that he can enjoy mealtimes and his life as fully and independently as any other child. We’re excited and hopeful to see where this goes.”

Paolo De Coppi, who is co-lead author of the paper, Consultant at GOSH and Head of Stem Cells and Regenerative Medicine at ICH said: “This is a major step forward for regenerative medicine, bringing us ever closer to treatment that goes beyond repairing damaged tissue and offers the possibility of rejection-free organs and tissues for transplant. At GOSH we see a large number of referrals for some of the most complex and rare defects of the gut, such as Hudson’s, and though the outlook for children like him is good, the condition and treatments have long-term implications.” The NIHR Research Professor also added: “We’re really excited about these promising preclinical findings. However, lots more research lies ahead before we can safely and effectively translate this approach to humans.

Study co-lead author Dr Paola Bonfanti, who is also a Group Leader at The Francis Crick Institute and Research Associate at ICH said: “This is the first time that such a complicated organ has been grown in the lab. Not only is the gut tube shaped, but as it also consists of several different layers of cells, which means we had to use a multi-step approach to develop a piece of oesophagus which resembles and works the same as a normal one. It’s truly a promising step forward for children and even adults with oesophageal conditions.”

Although still in its pre-clinical stage, research into tissue engineering such as this could lead to a new standard of care for patients with complex physical conditions especially in the case of children with damaged organs. The method avoids the need for a donated organ, which are often in short supply for the paediatric population and significantly lowers the risk of organ rejection.