Mesenchymal Stem Cell Therapy in Necrotizing Enterocolitis: A Rat Study

Abstract

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...

Current Research on the Epidemiology, Pathogenesis, and Management of Necrotizing Enterocolitis

“…Recent evidence from 3 different research groups has suggested that stem cells are able to influence the course of the disease in experimental NEC [88]: amniotic fluid stem (AFS) cells [89], mesenchymal stem cells [90,91], and enteric neural stem system cells [92]. In addition to the beneficial effects of AFS cells and the conditioned medium from AFS cells, other recent evidence highlights the potential role of factors in amniotic fluid in the prevention and/or treatment of NEC.…”

MSCS in Scenarios of Infection and Inflammation: Focus on Neonatal Diseases

“…These studies have not investigated the immunomodulatory role of MSCs in experimental NEC [106,107] (Table 2). Considering that the role of inflammation is paramount in the pathogenesis of NEC, it seems possible that the beneficial effects of MSCs in NEC models are mediated through an immunomodulatory role.…”

Stem Cell Therapies in Neonatology

“…The potential therapeutic use of bone marrow-derived MSCs in a rat model of NEC indicated that MSCs successfully homed to injured sites in the bowel and reduced pathological damage [41]. While, immunosuppressive activity of MSCs might well promote bacterial overgrowth and increase transmural bacterial translocation, further studies are necessary to examine long-term effects and risks of this approach.…”