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ABSTRACT:We evaluated the potential therapeutic use of exogenous human bone marrow-derived mesenchymal stem cells (hBMMSCs) in an experimental rat model of necrotizing enterocolitis (NEC). Thirty-six newborn Sprague-Dawley rats were randomly divided into three groups: NEC, NEC ϩ hBM-MSC, and a control (control and control ϩ hBM-MSC). NEC was induced by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. After NEC was induced, iron-labeled hBM-MSCs were administered by intraperitoneal injection. All pups were killed on the fourth day following injection, and the terminal ileum was excised for a histopathological and immunohistochemical evaluation. The pups in the NEC ϩ hBM-MSC group showed significant weight gains and improvements in their clinical sickness scores (p Ͻ 0.01). Bowel damage severity observed in the histopathological evaluation was significantly lower in the NEC ϩ hBM-MSC group than that in the NEC group (p ϭ 0.012). The number of MSCs homing to the bowel was significantly higher in the NEC ϩ hBM-MSC group than that in the control ϩ hBM-MSC group. In conclusion, this is the first study that has evaluated the effectiveness of hBM-MSCs in a neonatal rat NEC model. MSCs reduced histopathological damage significantly. (Pediatr Res 70: 489-494, 2011) N ecrotizing enterocolitis (NEC) is the most common gastrointestinal emergency and a leading cause of mortality and morbidity in newborn infants. The etiology and pathophysiology of NEC remains unclear. Although prematurity is the most consistent risk factor, hypoxic-ischemic injury, formula feeding, abnormal bacterial colonization, antenatal and postnatal risk components, and genetic aspects comprise other potential risk factors (1-3). Medical management of severe cases is often inadequate, and surgical intervention may be warranted. Thus, ϳ20 -40% of neonates eventually require a surgical procedure (1,4,5). In addition, morbid sequelae among survivors include impaired growth, short bowel syndrome, prolonged neonatal hospitalization, and poor longterm neurodevelopment (1-5). Therefore, the introduction of new strategies for the prevention and/or therapy for this devastating disease is essential to increase the survival rate and to reduce significant complications.Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into multiple cell types. In addition, MSCs secrete a wide variety of cytokines and chemokines that have beneficial paracrine actions during tissue repair (6 -11). Because of these unique properties, MSCs could be a future option for treating various diseases. Studies on the potential use of stem cells in pediatric diseases have recently aroused interest among clinicians (12-15), although stem cell therapy has not yet been studied as a treatment modality for neonatal intestinal disorders such as NEC. In this study, the therapeutic potential of exogenous human bone marrow-derived (hBM)-MSC therapy was evaluated in an experimental neonatal rat model of NEC. MATERIALS AND METHODSAnimal model. Fatih Uni...

Cord-blood 25(OH)D levels of neonates with EONS were significantly lower than that of the healthy controls, and a low level of cord-blood vitamin D was found to be associated with an increased risk of EONS. Further studies are warranted to confirm this association.

Erythropoietin (Epo) exerts neuroprotection against neuronal death induced by ischemia and hypoxia in vitro and in vivo. Recent studies suggest that the neuroprotective effects of Epo may depend upon different mechanisms, including the inhibition of nitric oxide (NO). We recently demonstrated that Epo exerts neuroprotection in a model of neonatal hypoxic-ischemic brain damage. In the present study, we directly determined whether systemic administration of recombinant Epo modulates cerebral NO production in a neonatal rat model of hypoxic-ischemic brain injury. Seven-day-old Wistar rat pups were subjected to left carotid artery occlusion followed by 2.5 h of hypoxic exposure. Brain nitrite levels were evaluated in both hemispheres (carotid ligated or nonligated) by Griess reagent 72 h after the hypoxic-ischemic insult. Our results show that hypoxic-ischemic insult results a significant increase in NO production as compared with NO levels in hypoxic hemispheres and control animals. A single dose of Epo treatment (1,000 U/kg i.p.) significantly decreased NO overproduction in the hypoxic-ischemic hemisphere, whereas no significant change appeared in hypoxia alone or in controls. These data suggest that the selective inhibitory effect of Epo on NO overproduction could have a neuroprotective effect in neonatal hypoxic-ischemic brain injury.

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