Gut instinct: Stem cell reactions

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  • Published: Apr 1, 2013
  • Author: David Bradley
  • Channels: MRI Spectroscopy
thumbnail image: Gut instinct: Stem cell reactions

NEC treatment

Villi from NHS press release -

In research funded by Great Ormond Street Hospital Children's Charity and with support from the Fondazione Citta della Speranza, researchers have demonstrated that stem cells taken from amniotic fluid can be used to restore gut structure and function following intestinal damage in rodents. The new work published in the journal Gut uses magnetic resonance imaging and could pave the way to a new form of cell therapy that is able to reverse serious damage caused by inflammation in the intestines of babies.

Necrotizing enterocolitis (NEC) is a medical condition seen in premature infants, portions of the bowel undergo tissue death. Feeding intolerance, increased gastric residuals, abdominal distension and bloody stools are the first signs, although symptoms appear later, the earlier the baby is born. Ultimately, intestinal perforation and peritonitis occurs and systemic hypotension, all of which require intensive medical support. An infectious agent is suspected but not proven and a link with infection by Pseudomonas aeruginosa is known. This causes NEC in both premature infants and neutropaenic cancer patients. Treatment involves standard intensive care but there are various feeding regimens, basically tiny amounts of breast milk and probiotics given orally. These are thought to reduce the risk of the condition developing further, although surgery is often inevitable and leads to shortening of the bowel and intestinal failure requiring transplant. Premature infants commonly have other problems, but if NEC is treated the survival rate can be increased.

UCL working with AFS for NEC

New work led by the UCL Institute of Child Health, has turned to amniotic fluid stem (AFS) cells to test whether they might be used to treat NEC early in a rat model. Comparison with NEC-affected rats given bone marrow stem cells taken from their femurs, or fed as normal with no treatment, were used as controls for the tests.

The team found that NEC-affected rats injected with AFS cells showed significantly higher survival rates a week after being treated, compared to the other two groups. Inspection of their intestines, using micro magnetic resonance imaging (MRI), showed the degree of inflammation in the intestinal tissues to be significantly reduced, with fewer dead cells, greater self-renewal of the gut tissue and better overall intestinal function. The team also utilised gas chromatography-mass spectrometry in their study, says team member Simon Eaton.

Previously, bone marrow stem cells have been used in efforts to reverse colonic damage caused by irritable bowel disease and do regenerate tissue, but the rat model shows them not to be beneficial in NEC. The assumption is that a different mechanism is invoked when the AFS cells are used instead. The team explains that following injection of AFS cells into the rat gut, the cells migrate into the intestinal villi - the small, finger-like projections that protrude from the lining of the intestinal wall and pass nutrients from the intestine into the blood. However, instead of then simply acting to repair the damaged tissue, the AFS cells seem to release specific growth factors that then act on progenitor cells in the gut so reducing inflammation and triggering the formation of new villi and other tissues.

Future malformations

Study leader Paolo De Coppi explains: "Stem cells are well known to have anti-inflammatory effects, but this is the first time we have shown that amniotic fluid stem cells can repair damage in the intestines. In the future, we hope that stem cells found in amniotic fluid will be used more widely in therapies and in research, particularly for the treatment of congenital malformations. Although amniotic fluid stem cells have a more limited capacity to develop into different cell types than those from the embryo, they nevertheless show promise for many parts of the body including the liver, muscle and nervous system."

De Coppi told SpectroscopyNOW that the team is now intending to move in a new direction. "We are moving away from the cells: since we know the cells are activating resident stem cells in the intestine we want to understand which molecules the amniotic fluid stem cells secrete and use them instead," he explains. "This is a long-term plan and it may not work because the cells may secrete multiple factors in response to the local inflammation and this may results difficult to mimic." He adds that in the long term, the research will need to be carried out in larger mammals, such as porcine model, before any tests can begin in people.

Related Links

Gut 2013, online: "Amniotic fluid stem cells improve survival and enhance repair of damaged intestine in NEC via a COX-2 dependent mechanism"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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