‘World’s first lab-grown oesophagus implanted in mice’

In a first, scientists say they have grown functional sections of oesophagus in the lab using stem cells and successfully transplanted them into mice.

The advance, published in the journal Nature Communications, offers a potential path towards developing treatments for children with oesophageal defects.

The study by researchers at the Francis Crick Institute in the UK and colleagues is the first of its kind for a complex multi-layered organ, overcoming a major challenge of regenerative medicine: different early-stage cells need different conditions to develop into the right cell type.

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“We were amazed to see that our engineered tissue had both the structure and function of a healthy oesophagus, and hooked up with nearby blood vessels within a week of transplantation—a promising step forward in our pursuit to create better treatments for patients with oesophageal defects,” said Paola Bonfanti from the Francis Crick Institute.

The team engineered pieces of oesophagus—about two centimetres in length—by injecting different stem cells into rat tissue scaffolds, in stages, under the optimum conditions for each cell type.

First, they injected early-stage connective tissue and muscle cells from mice and humans into the scaffold, which formed muscle layers when the scaffold was made to mimic the movements of an oesophagus.

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Next, they injected mouse early-nerve cells, which formed neurons that innervated the muscle layers.

Finally, the researchers injected rat early-epithelial cells which formed a functional cell barrier lining the inside of the oesophagus.

They used stem cells from different species so that they could check which tissues were derived from which cells.

“To our surprise, in a relatively short amount of time, the stem cells we injected on the oesophagus scaffold matured into fully functional cells,” said researcher Luca Urbani.

When complete, the mini oesophagi had all the right layers of different cell types, were capable of muscle contraction—needed to move food down to the stomach—and could be preserved at low temperatures.

This opens up the possibility of mass-producing and storing them ready for transplantation, if this approach were to be scaled-up for patients in the clinic.

When the team transplanted the oesophagi into a fatty sheet of tissue in the mouse abdomen, known as the omentum, they formed a functional blood supply, crucial for cell survival.

The omentum was chosen as the site of transplantation because it is easier to operate on the abdomen of small animals, like mice, that the upper chest, researchers said.

The omentum also has a rich blood supply which helps transplanted organs survive, they 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,” said Paolo De Coppi from the University College London (UCL) in the UK.