“Mini organs” grown using stem cells from a patient’s tissue could offer hope for children with intestinal failure, a study suggests.
Scientists at the Francis Crick Institute, Great Ormond Street Hospital (GOSH) and UCL Great Ormond Street Institute of Child Health (ICH) have grown human intestinal grafts using stem cells from patient tissue. The team hope the findings could one day lead to personalised transplants for children with intestinal failure.
Dr Vivian Li, senior author and group leader of the Stem Cell and Cancer Biology Laboratory at the Crick, said: “It’s urgent that we find new ways to care for children without a working intestine because, as they grow older, complications from parenteral [intravenous] nutrition can arise.
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“We’ve set out a process to grow one layer of intestine in the laboratory, moving us a step closer to being able to offer these patients a form of regenerative medicine, which uses materials created from their own tissue.
“This would reduce some of the risks that transplant patients face, such as their immune system attacking the transplant.”
Children with intestinal failure cannot absorb the nutrients essential for their overall health and development, researchers said.
While they can be fed intravenously, via a process called parenteral nutrition, this is associated with “severe” complications such as line infections and liver failure, they added.
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If complications arise, or in severe cases the children need a transplant, researchers said there is a shortage of suitable donor organs and problems can arise after surgery – such as the body rejecting the transplant.
The “proof-of-concept” study, published in Nature Medicine on Monday, showed how intestinal stem cells and small intestinal or colonic tissue taken from patients can be used to grow the inner layer of small intestine in the laboratory with the capacity to digest and absorb peptides and digest sucrose in food.
The researchers took small biopsies of intestine from 12 children who either had intestinal failure or were at risk of developing the condition. In the lab they then stimulated the biopsy cells to grow into “mini-guts”, also known as intestinal organoids, generating over 10 million intestinal stem cells from each patient over the course of four weeks.
The researchers also collected small intestine and colon tissue that would have been discarded from other children undergoing essential surgery to remove parts of their gut.
Using laboratory techniques cells were removed from these tissues leaving behind a skeleton structure which formed scaffolds. The researchers placed the “mini-guts” onto these scaffolds where they grew on this structure to form a living graft.
Due to specific culture conditions, the stem cells changed into many of the different types of cells that exist in the small intestine and the grafts were able to digest and absorb peptides, the building blocks of proteins, as well as digest sucrose into glucose sugars.
The authors said research was the first step in efforts to engineer all the layers of the intestine for transplantation in the hope that laboratory-grown organs could offer a safe and longer-lasting alternative to traditional donor transplants.
Senior author Professor Paolo De Coppi, consultant paediatric surgeon at GOSH, said the research was an “important step forward in regenerative medicine”.
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He added: “Although this research is in the lab right now, we’re concentrating on making this a realistic and safe treatment option. What’s significant here is we’ve shown that scaffolds can be created using tissue from the colon, not only tissue from the small intestine.
“It’s an important step forward in regenerative medicine and we’re optimistic about what this means for patients, but more research lies ahead before we can safely and effectively translate this approach to treatment.”
As well as proving that biopsies taken from children could be used to grow functioning intestinal grafts, the researchers said that the grafts can survive and mature when transplanted into mice. Researchers said the next step was to start growing the other layers of the intestine such as muscle and blood vessels.
Reader Q&A: How many organs in the body could you live without?
Asked by: Alicia Jones, Maidstone
You can still have a fairly normal life without one of your lungs, a kidney, your spleen, appendix, gall bladder, adenoids, tonsils, plus some of your lymph nodes, the fibula bones from each leg and six of your ribs. Losing your uterus, ovaries and breasts, or your testicles and prostate, is also quite survivable, although you might need hormone therapy to avoid other long-term problems, such as brittle bones.
If you allow yourself artificial replacements and medication, we can go further and remove your stomach, colon, pancreas, salivary glands, thyroid, bladder and your other kidney. Still not enough for you? Theoretically, surgeons could amputate all of your limbs, and remove your eyes, nose, ears, larynx, tongue, lower spine and rectum. Supported by machines in an intensive care unit, they could also take away your skull, heart and your remaining lung, at least for a short while.
This adds up to a theoretically survivable loss of around 45 per cent of your total body mass. But any trauma that destroyed all these organs all at once would almost certainly kill you from shock and blood loss. And surgically removing them one at a time over many months would likely also be fatal, due to infections in your immune-compromised state.
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