Animal models of necrotizing enterocolitis: review of the literature and state of the art

Sulistyo, Adrienne; Rahman, Abidur; Biouss, George; Antounians, Lina; Zani, Augusto

doi:10.1515/iss-2017-0050

Cited by 18 publications

(30 citation statements)

References 44 publications

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“…In Barlow’s model, a formula was developed which simulated rat breast milk and could be mixed with a bacterial contaminant. In this model, the pups are removed immediately after Cesarian section and are placed in an incubator, with avoidance of breast feeding 8. The stressors used to induce a NEC like state in the animal models includes hypoxia, hypothermia, addition of a lipopolysaccharide (LPS) and hyperosmolar formula during the course of feeding throughout a week long experiment (figure 1).…”

Section: Animal Modelsmentioning

confidence: 99%

“…The stressors used to induce a NEC like state in the animal models includes hypoxia, hypothermia, addition of a lipopolysaccharide (LPS) and hyperosmolar formula during the course of feeding throughout a week long experiment (figure 1). In this model, a formula is given four times per day with an increasing caloric intake each day of the week 8. At the end of the protocol, or when rat pups have clinical signs of NEC, intestines are harvested and histologically graded for intestinal injury 0–4 with lessions greater than 2 being considered as NEC (figure 2).…”

Section: Animal Modelsmentioning

confidence: 99%

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Animal models of necrotizing enterocolitis

Mendez

Khan

Perrier

et al. 2020

World Jnl Ped Surgery

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BackgroundNecrotizing enterocolitis (NEC) is one of the leading causes of death in premature infants. To determine the factors present in the disease that lead to increased morbidity and mortality, manipulation of variables that are shown to have a positive response has been tested using various animal models. Testing and manipulation of these variables are unwarranted in humans due to regulatory health standards.MethodsThe purpose of this review is to provide an update to previous summaries that determine the significance of animal models in studying the mechanisms of NEC. A large variety of animal models including rats, mice, rabbits, piglets, nonhuman primates, and quails have been described in literature. We reviewed the reported animal models of NEC and examined the pros and cons of the various models as well as the scientific question addressed.ResultsThe animals used in these experiments were subject to gavage feeding, hypoxia, hypothermia, oxygen perfusion, and other methods to induce the disease state. Each of these models has been utilized to show the effects of NEC on the premature, undeveloped gut in animals to find a correlation to the disease state present in humans. We found specific advantages and disadvantages for each model.ConclusionsRecent advances in our understanding of NEC and the ongoing therapeutic strategy developments underscore the importance of animal models for this disease.

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Section: Animal Modelsmentioning

confidence: 99%

Section: Animal Modelsmentioning

confidence: 99%

Animal models of necrotizing enterocolitis

Mendez

Khan

Perrier

et al. 2020

World Jnl Ped Surgery

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show abstract

Section: Introductionmentioning

confidence: 99%

“…A number of animal models have been developed to investigate the pathophysiology of NEC and to test different preventive and therapeutic strategies (12)(13)(14)(15)(16)(17)(18). The most widely used experimental animals are rats, mice, and piglets (12)(13)(14)(15)(16)(17)(18). The experimental models try to reproduce the pathogenesis of NEC using one or a combination of potential contributory factors such as intestinal immaturity, formula feeding, bacteria and/or their byproduct, and hypoxic-ischemic stress (12)(13)(14)(15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

“…The most widely used experimental animals are rats, mice, and piglets (12)(13)(14)(15)(16)(17)(18). The experimental models try to reproduce the pathogenesis of NEC using one or a combination of potential contributory factors such as intestinal immaturity, formula feeding, bacteria and/or their byproduct, and hypoxic-ischemic stress (12)(13)(14)(15)(16)(17)(18). However, after more than five decades of preclinical and clinical research on NEC, the promise of a "magic bullet" for the prevention and/or treatment of NEC has yet to become a reality (11).…”

Section: Introductionmentioning

confidence: 99%

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Stem Cells as Therapy for Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis of Preclinical Studies

et al. 2020

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Background: Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal condition among very and extremely preterm infants. Stem cell therapy has shown some promising protective effects in animal models of intestinal injury, including NEC, but no systematic review has yet evaluated the preclinical evidence of stem cell therapy for NEC prevention or treatment.Methods: PubMed and EMBASE databases were searched for studies using an animal model of NEC with stem cells or their products. The SYRCLE tool was used for the assessment of risk of bias. A random-effects model was used to pool odds ratios (ORs) and 95% confidence interval (CI).Results: We screened 953 studies, of which nine (eight rat and one mouse models) met the inclusion criteria. All animal models induced NEC by a combination of hypothermia, hypoxia, and formula feeding. Risk of bias was evaluated as unclear on most items for all studies included. Meta-analysis found that both mesenchymal and neural stem cells and stem cell-derived exosomes reduced the incidence of all NEC (OR 0.22, 95% CI 0.16–0.32, k = 16), grade 2 NEC (OR 0.41, 95% CI 0.24–0.70, k = 16), and grade 3–4 NEC (OR 0.28, 95% CI 0.19–0.42, k = 16). k represents the number of independent effect sizes included in each meta-analysis. The effect of the exosomes was similar to that of the stem cells. Stem cells and exosomes also improved 4-day survival (OR 2.89 95% CI 2.07–4.04, k = 9) and 7-day survival (OR 3.96 95% CI 2.39–6.55, k = 5) after experimental NEC. Meta-analysis also found that stem cells reduced other indicators of intestinal injury.Conclusion: The data from this meta-analysis suggest that both stem cells and stem cell-derived exosomes prevented NEC in rodent experimental models. However, unclear risk of bias and incomplete reporting underline that poor reporting standards are common and hamper the reliable interpretation of preclinical evidence for stem cell therapy for NEC.

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Necrotizing Enterocolitis: A Multi-omic Approach and the Role of the Microbiome

Neu

2020

Dig Dis Sci

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Necrotizing enterocolitis (NEC) is a poorly defined disease that primarily affects preterm infants. There has not been much progress in the prevention or treatment of NEC since it became recognized as a common problem in preterm infants. Reasons for this lack of progress include the likelihood that different diseases are being put under the same moniker of "NEC," similar to using "diabetes" for the different diseases it represents. In order to make progress, better delineation of the phenotypes that present as NEC will be necessary to clearly establish their pathophysiology, find specific and sensitive biomarkers, and establish preventative regimens. In this review, we summarize some of the entities that are being called NEC, discuss the pathophysiology of the most classic form of NEC, and provide an overview of how we might proceed in the future to make progress in this field.

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Animal models of necrotizing enterocolitis: review of the literature and state of the art

Cited by 18 publications

References 44 publications

Animal models of necrotizing enterocolitis

Animal models of necrotizing enterocolitis

Stem Cells as Therapy for Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis of Preclinical Studies

Necrotizing Enterocolitis: A Multi-omic Approach and the Role of the Microbiome

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