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.

Severe COVID‐19 infection results in bilateral interstitial pneumonia, often leading to acute respiratory distress syndrome (ARDS) and pulmonary fibrosis in survivors. Most patients with severe COVID‐19 infections who died had developed ARDS. Currently, ARDS is treated with supportive measures, but regenerative medicine approaches including extracellular vesicle (EV)‐based therapies have shown promise. Herein, we aimed to analyse whether EV‐based therapies could be effective in treating severe pulmonary conditions that affect COVID‐19 patients and to understand their relevance for an eventual therapeutic application to human patients. Using a defined search strategy, we conducted a systematic review of the literature and found 39 articles (2014–2020) that reported effects of EVs, mainly derived from stem cells, in lung injury models (one large animal study, none in human). EV treatment resulted in: (1) attenuation of inflammation (reduction of pro‐inflammatory cytokines and neutrophil infiltration, M2 macrophage polarization); (2) regeneration of alveolar epithelium (decreased apoptosis and stimulation of surfactant production); (3) repair of microvascular permeability (increased endothelial cell junction proteins); (4) prevention of fibrosis (reduced fibrin production). These effects were mediated by the release of EV cargo and identified factors including miRs‐126, −30b‐3p, −145, −27a‐3p, syndecan‐1, hepatocyte growth factor and angiopoietin‐1. This review indicates that EV‐based therapies hold great potential for COVID‐19 related lung injuries as they target multiple pathways and enhance tissue regeneration. However, before translating EV therapies into human clinical trials, efforts should be directed at developing good manufacturing practice solutions for EVs and testing optimal dosage and administration route in large animal models.

Aim To determine (1) the incidence of neurodevelopmental impairment (NDI) in necrotising enterocolitis (NEC), (2) the impact of NEC severity on NDI in these babies and (3) the cerebral lesions found in babies with NEC. Methods Systematic review: three independent investigators searched for studies reporting infants with NDI and a history of NEC (PubMed, Medline, Cochrane Collaboration, Scopus). Meta-analysis: using RevMan V.5.3, we compared NDI incidence and type of cerebral lesions between NEC infants versus preterm infants and infants with medical vs surgical NEC. Results Of 10 674 abstracts screened, 203 full-text articles were examined. In 31 studies (n=2403 infants with NEC), NDI incidence was 40% (IQR 28%–64%) and was higher in infants with surgically treated NEC (43%) compared with medically managed NEC (27%, p<0.00001). The most common NDI in NEC was cerebral palsy (18%). Cerebral lesions: intraventricular haemorrhage (IVH) was more common in NEC babies (26%) compared with preterm infants (18%; p<0.0001). There was no difference in IVH incidence between infants with surgical NEC (25%) and those treated medically (20%; p=0.4). The incidence of periventricular leukomalacia (PVL) was significantly increased in infants with NEC (11%) compared with preterm infants (5%; p<0.00001). Conclusions This study shows that a large proportion of NEC survivors has NDI. NEC babies are at higher risk of developing IVH and/or PVL than babies with prematurity alone. The degree of NDI seems to correlate to the severity of gut damage, with a worse status in infants with surgical NEC compared with those with medical NEC. Trial registration number CRD42019120522.