Treatment of necrotizing enterocolitis (NEC) with amniotic fluid stem cells

Abstract

Necrotizing enterocolitis (NEC) is a devastating disease of newborn infants, characterized by necrosis of one or more portions of the small and/or large bowel. Despite extensive research and advancement in medical and surgical treatment over the last six decades, NEC still represents a challenging condition with a mortality rate as high as 40 % especially in very low birth weight infants. Stem cell therapy has become an option for other intestinal diseases, such as refractory Crohn's disease, which share some features with NEC. We first attempted administration of amniotic fluid stem (AFS) cells in a well-established neonatal rat model of NEC. In this study, AFS cells integrated in the bowel wall and improved rat survival and clinical conditions, decreased NEC incidence and macroscopic gut damage, improved intestinal function, decreased bowel inflammation, increased enterocyte proliferation and reduced apoptosis. The beneficial effect was achieved via modulation of stromal cells expressing cyclooxygenase 2 in the lamina propria. Moreover, AFS cells differentially expressed genes of the Wnt/β-catenin pathway, which regulate intestinal epithelial stem cell function and cell migration and growth factors known to maintain gut epithelial integrity and reduce mucosal injury. The same beneficial effects of the amniotic fluid have been later confirmed by other authors using different experimental models of NEC. Stem cell therapy may represent a new therapeutic option for children with NEC. Understanding the mechanism of action of AFS cells in experimental NEC may help the development of new cellular or pharmacological therapies for human infants with NEC.