March 25, 2013
Stem Cells Heal Damaged Intestinal Tissue In Premature Babies
Lawrence LeBlond for redOrbit.com - Your Universe Online
Researchers studying stem cells removed from amniotic fluid have found a possible role the cells have on healing damage caused by necrotizing enterocolitis (NEC), a severe inflammation that can destroy tissues in the gut and lead to major organ failure.
The study was funded by Great Ormond Street Hospital (GOSH) Children´s Charity and led by University College London´s (UCL) Institute of Child Health (ICH). The researchers investigated how the stem cells work in relation to NEC, which is the most common gastrointestinal surgical emergency in newborns, with mortality rates or around 15 to 30 percent in the UK.
While breast milk and probiotics are known to offer some level of protection against NEC, there are currently no medical treatments available other than emergency surgery. Surgical removal, however, shortens the bowel and can lead to intestinal failure, with some babies needing ongoing intravenous nutrition or intestinal transplant.
Babies born prematurely often have guts that are ill-prepared to handle food, and about one in 10 preemies in neonatal intensive care go on to develop NEC. The inflammation can cause tissue death and lead to holes in the intestine which can lead to even more serious infections.
"It is quite a problem and we think it is on the increase," said Dr. Simon Eaton, from UCL´s Institute of Child Health.
Dr. Eaton, who was part of the research team investigating the role of amniotic stem cells in laboratory rats programmed to develop fatal NEC, said the injections of the stem cells appeared to increase the survival times of the rats.
"We're able to prolong survival by quite a long way,” he told the BBC. "What appears to be happening is a direct effect on calming inflammation and also stimulating resident stem cells in the gut to be more efficient at repairing the intestines."
The researchers harvested amniotic fluid stem (AFS) cells from rodent amniotic fluid and injected them into rats with NEC. Other rats with the same condition were given bone marrow stem cells taken from their femurs, or were kept on normal nutrition with no treatment, to compare clinical outcomes.
The rats injected with AFS cells showed significantly higher survival rates a week after given the treatment, compared to the other two groups. Upon further inspection of their intestines, the researchers found inflammation was significantly reduced, with fewer dead cells, greater self-renewal of gut tissue and better overall intestinal function.
The researchers noted that bone marrow stem cells have been shown in the past to reverse colonic damage in irritable bowel syndrome, but the beneficial effects from bone marrow did not spill over into NEC therapy, indicating different mechanisms were at play for NEC. Following the injections of AFS cells into the gut, the cells moved into the intestinal villi — small, finger-like projections that protrude from the lining of the intestinal wall which pass nutrients from the intestine to the blood.
The researchers found that instead of directly repairing the damaged tissue, the AFS cells appeared to release specific growth factors that acted on progenitor cells in the gut which in turn, reduced inflammation and triggered the formation of new villi.
"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,” said lead author Dr. Paolo De Coppi, of UCL´s Institute of Child Health.
“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," he added.
"Once we have a better understanding of the mechanisms by which AFS cells trigger repair and restore function in the gut, we can start to explore new cellular or pharmacological therapies for infants with necrotizing enterocolitis," noted Dr. Eaton.
Before the research can be tested in human premature babies, the researchers said far more testing is needed to ensure it would be a safe treatment option. Stem cells would have to be taken from a donor as it would not be practical to store fluid from every birth. And with donor cells, there runs the risk of rejection.
Also, there is a risk that the stem cells can become other types of cells posing a risk of developing cancer.
The researchers hope that in the future, if the treatment is proven viable, a drug can be harnessed from the AFS cells.
"It's not the cells, they're delivering something and if we knew what that was then we could deliver that directly," Dr. Eaton told the BBC´s James Gallagher.