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Necrotising enterocolitis treated with hPSC therapy

Tue, 04/27/2021 - 14:58
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Scientists at the Wake Forest Institute for Regenerative Medicine (WFIRM) are treating necrotising enterocolitis with a human placental-derived stem cell (hPSC) therapy strategy that is showing promising results, they reported that stem cell therapy promoted healing of the intestinal damage at both the cellular and whole tissue levels.

"In our recent studies, we demonstrated that a promising placental stem cell therapy could induce repair of established damage caused by the disease. Interestingly, we saw that the predominate repair occurred in the barrier cells that line the intestine, which presents a potential new therapeutic target," said Dr Victoria G Weis and lead author of the paper, ‘Human placental-derived stem cell therapy ameliorates experimental necrotizing enterocolitis’, published in the American Journal of Physiology-Gastrointestinal and Liver Physiology.

Necrotising enterocolitis is a life-threatening intestinal disease that is a leading cause of mortality in premature infants and treatment options remain elusive. It affects up to 10 percent of premature infants at a very vulnerable and developmentally crucial time can lead to serious infection and death.

The cause of the disease is unclear - it is a multi-faceted disease that results from the complex interaction of early bacterial colonisation, an exaggerated inflammatory response, and immature intestinal tissue. It occurs when the wall of the intestine is invaded by bacteria which cause infection and inflammation. Developing treatment approaches for this disease would improve both the survival outcomes and the health of these children who have their entire lifetime to protect.

Based on recent cell therapy studies, WFIRM scientists investigated the effect of a human placental-derived stem cell therapy on intestinal damage in a pre-clinical animal model. In 2007, WFIRM scientists were the first to identify and characterize stem cells derived from amniotic fluid and placenta. Stem cells offer great promise for new medical treatments to treat disease and injury.

In the last decade, researchers have made significant advances in identifying important prevention strategies for reducing the risk of necrotizing enterocolitis onset. Unfortunately, few approaches have demonstrated the therapeutic ability to offset established damage. To address this gap, the researchers focused their study on the potential of human placental-derived stem cells for treatment.

For the study, the pre-clinical model with induced intestinal damage received injections of either saline or the placental stem cell therapy at 32 and 56 hours following birth directly into the abdominal cavity. At four days, the induced damage was assessed. The researchers found that the placental stem cell therapy stopped disease progression and promoted healing of the intestinal damage at both the cellular and whole tissue levels.

One of the most prominent findings in the study is the significant improvement of the two critical cell populations that are important to the intestine's ability to continuously replenish and sustain the barrier. In necrotising enterocolitis disease, these intestinal cell populations are significantly lost and the function of the intestinal barrier is drastically compromised. The placental stem cell treatment helped support the re-establishment of these cell populations to healthy levels which allow the intestine to properly form a functioning barrier against further bacterial infection.

"These findings open exciting new avenues for advanced therapeutic development that could hopefully one day contribute to the advancement of medical care for this disease and help set the foundation for a long and healthy life for these babies," added Weis.

Senior study author, Dr Anthony Atala, director of WFIRM, said that human placental-derived stem cells are a novel research tool that can be leveraged to identify ways to repair damage or combat disease altogether. "Our results show that stem cell treatment can promote intestinal healing. In this disease model, utilizing them as an early intervention may be better tolerated in the infant and, further, may decrease disease progression to advanced stages that require surgery.”

To access this paper, please click here