Amniotic fluid stem cells improve survival and enhance repair of damaged intestine in necrotising enterocolitis via a COX-2 dependent mechanism

Abstract

Objective: Necrotising enterocolitis (NEC) remains one of the primary causes of morbidity and mortality in neonates and alternative strategies are needed. Stem cells have become a therapeutic option for other intestinal diseases, which share some features with NEC. We tested the hypothesis that amniotic fluid stem (AFS) cells exerted a beneficial effect in a neonatal rat model of NEC. Design: Rats intraperitoneally injected with AFS cells and their controls (bone marrow mesenchymal stem cells, myoblast) were analysed for survival, behaviour, bowel imaging (MRI scan), histology, bowel absorption and motility, immunofluorescence for AFS cell detection, degree of gut inflammation (myeloperoxidase and malondialdehyde), and enterocyte apoptosis and proliferation. Results: 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, as shown by survival studies using selective and non-selective cyclooxygenase 2 inhibitors. Interestingly, 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. Conclusions: We demonstrated here for the first time that AFS cells injected in an established model of NEC improve survival, clinical status, gut structure and function. Understanding the mechanism of this effect may help us to develop new cellular or pharmacological therapies for infants with NEC

Necrotizing enterocolitis: current perspectives

“…130 Amniotic fluid stem cells injected intraperitoneally resulted in improved survival, decreased the incidence of NEC, and improved the macroscopic appearance and function of the gastrointestinal tract. Use of stem cells in clinical neonatology may not be very close, but is one of the therapeutic options with huge potential, and needs further trials to establish its safety and efficacy.…”

Stem Cell Therapy in the Treatment of Inflammatory Bowel Disease

“…Another mechanism of therapeutic effect of MSC is their prominent regenerative effect as these cells are the precursors of the connective tissue [14,15,19]. MSC were revealed to release numerous trophic factors (VEGF, EGF etc) and affect all stages of the complex process of wound healing -inflammatory, proliferative and tissue remodeling [21].…”

“…The application of nanoparticles for the transportation of drugs despite its high cost is also promising [2]. potential and effectiveness of SC in the treatment of UC and CD [7,[9][10][11]14,15]. According to experts' prognoses, CT will become the next generation of therapeutic arrangements in the treatment of IBD, in particular for patients with the secondary resistance to anticytokine therapy [4,12].…”

Stem cell therapy in inflammatory bowel disease: A promising therapeutic strategy?

“…Recently, AFSCs were used in a neonatal rat model of necrotizing enterocolitis, one of the primary causes of morbidity and mortality in neonates, showed a decrease in intestinal damage, an increase in gut tissue repair and a higher survival [59,60] . A better understanding of the AFSCs biology and mechanisms of action may help to develop strategies for their use in other IBD.…”