Necrotizing enterocolitis (NEC), a condition where sections of the bowel undergo tissue death, is a common cause of mortality and morbidity in neonates, particularly those born prematurely. Even after successful treatment of the acute stage of the disease, survivors can be left with complications relating to intestinal dysmotility. New research published in Stem Cell Research & Therapy by Gail Besner from the Ohio State University College of Medicine, USA, and colleagues suggests that stem cells may provide a future treatment option for these long term complications.
Although the pathophysiology of NEC is not fully understood, prematurity is known to be a major risk factor. The enteric nervous system (ENS), part of the autonomic nervous system, contains two major nerve plexuses (the myenteric and submucosal plexus) that control the gastrointestinal system. The ENS is not fully developed at birth, and is more immature in premature neonates. During early neonatal life it undergoes neuroplasticity. The immaturity of the ENS is thought to contribute to the development of NEC, and damage to the ENS during the disease could be the cause of persistent intestinal dysmotility.
The researchers demonstrate that significant injury to the ENS occurs during NEC. Their findings also suggest that neural stem cell transplantation may provide a novel future treatment. Specimens of human intestine were obtained from neonates with NEC and controls (with bowel atresia) who were undergoing bowel resection and subsequent stoma closure. Examination of the NEC specimens showed significant damage to the ENS compared to controls. Furthermore, the structural and functional changes to the intestine were still present several months later when the stomas were closed.
In order to test whether stem cell treatment could be beneficial, the researchers used a rat pup model of NEC that exhibits similar abnormalities to those observed in the human NEC specimens. They administered neural stem cells after initial recovery from NEC and found that the transplanted cells differentiated into functional neurons. Moreover, compared to control pups, those receiving the transplant had decreased mortality, improved intestinal motility and improved ENS and intestinal integrity.
These results support the theory that significant damage occurs in the ENS during NEC and suggest that transplantation of neural stem cells could provide a novel treatment for NEC.