Mini-organs could offer treatment hope for children with intestinal
failure

Date:
September 8, 2020
Source:
The Francis Crick Institute
Summary:
Scientists have grown human intestinal grafts using stem cells from
patient tissue that could one day lead to personalized transplants
for children with intestinal failure.



FULL STORY ========================================================================== Pioneering 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 that could one day lead to personalised transplants for children
with intestinal failure, according to a study published in Nature Medicine today (Monday 7th September).


========================================================================== Children with intestinal failure cannot absorb the nutrients that are
essential for their overall health and development. This may be due to
a disease or injury to their small intestine.

In these cases, children can be fed intravenously via a process called parenteral nutrition, however this is associated with severe complications
such as line infections and liver failure. If complications arise or in
severe cases these children may need a transplant. However, there is a
shortage of suitable donor organs and problems can arise after surgery,
such as the body rejecting the transplant.

In their proof-of-concept study, the research team showed how intestinal
stem cells and small intestinal or colonic tissue taken from patients
can be used to grow the important inner layer of small intestine in the laboratory with the capacity to digest and absorb peptides and digest
sucrose in food.

This is the first step in efforts to engineer all the layers of the
intestine for transplantation. The researchers hope that one day,
laboratory grown organs could offer a safe and longer-lasting alternative
to traditional donor transplants.

"It's urgent that we find new ways to care for children without a working intestine because, as they grow older, complications from parental
nutrition can arise," says Dr Vivian Li, senior author and group leader
of the Stem Cell and Cancer Biology Laboratory at the Crick.



========================================================================== "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." 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 4 weeks.

The researchers also collected small intestine and colon tissue, that
would otherwise 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. The grafts were able to digest
and absorb peptides, the building blocks of proteins, as well as digest
sucrose into glucose sugars.

"Although this research is in the lab right now, we're concentrating
on making this a realistic and safe treatment option," explains senior
author NIHR Professor Paolo De Coppi, Consultant Paediatric Surgeon at
GOSH and Head of Surgery, Stem Cells & Regenerative Medicine Section at
the UCL Great Ormond Street Institute of Child Health (ICH).

"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. In practice, it is often easier to obtain tissue from the colon, so this
could make the approach much more feasible. 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 also demonstrated that the grafts
survive and mature when transplanted into mice.

"By applying our basic science knowledge of intestinal stem cell biology,
we have developed a time efficient and clinically relevant method for rebuilding human small intestine grafts for transplantation," says Laween Meran, lead author, Gastroenterology Registrar and Clinical Research
Training Fellow at the Stem Cell and Cancer Biology Laboratory at the
Crick and the ICH.

"Now that we've shown the grafts are successful on a small scale, the
next crucial steps will be to start growing the other layers of the
intestine such as muscle and blood vessels, whilst also scaling up our
methods to create viable grafts relevant to individual patient needs."

========================================================================== Story Source: Materials provided by The_Francis_Crick_Institute. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Laween Meran, Isobel Massie, Sara Campinoti, Anne E. Weston, Riana
Gaifulina, Lucinda Tullie, Peter Faull, Michael Orford, Anna
Kucharska, Anna Baulies, Laura Novellasdemunt, Nikolaos Angelis,
Elizabeth Hirst, Julia Ko"nig, Alfonso Maria Tedeschi, Alessandro
Filippo Pellegata, Susanna Eli, Ambrosius P. Snijders, Lucy
Collinson, Nikhil Thapar, Geraint M. H. Thomas, Simon Eaton,
Paola Bonfanti, Paolo De Coppi, Vivian S. W. Li. Engineering
transplantable jejunal mucosal grafts using patient-derived
organoids from children with intestinal failure. Nature Medicine,
2020; DOI: 10.1038/s41591-020-1024-z ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200908113253.htm

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