Human bone marrow-derived mesenchymal stromal cells reduce the severity of experimental necrotizing enterocolitis in a concentration-dependent manner
Keywords: 
Materias Investigacion::Ciencias de la Salud::Pediatría
Necrotizing enterocolitis
Neonate
Inflammation
Human bone marrow mesenchymal stromal cells
Mouse model
Apoptosis
Zonula occludens-1
Interleukin 1b
Caspase 3
Issue Date: 
2023
Publisher: 
MDPI
ISSN: 
2073-4409
Note: 
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license
Citation: 
Provitera, L. (Livia); Tomaselli, A. (Andrea); Raffaeli, G. (Genny); et al. "Human bone marrow-derived mesenchymal stromal cells reduce the severity of experimental necrotizing enterocolitis in a concentration-dependent manner". Cells. 12 (5), 2023, 760
Abstract
: Necrotizing enterocolitis (NEC) is a devastating gut disease in preterm neonates. In NEC animal models, mesenchymal stromal cells (MSCs) administration has reduced the incidence and severity of NEC. We developed and characterized a novel mouse model of NEC to evaluate the effect of human bone marrow-derived MSCs (hBM-MSCs) in tissue regeneration and epithelial gut repair. NEC was induced in C57BL/6 mouse pups at postnatal days (PND) 3–6 by (A) gavage feeding term infant formula, (B) hypoxia/hypothermia, and (C) lipopolysaccharide. Intraperitoneal injections of PBS or two hBM-MSCs doses (0.5 × 106 or 1 × 106 ) were given on PND2. At PND 6, we harvested intestine samples from all groups. The NEC group showed an incidence of NEC of 50% compared with controls (p < 0.001). Severity of bowel damage was reduced by hBM-MSCs compared to the PBS-treated NEC group in a concentration-dependent manner, with hBM-MSCs (1 × 106 ) inducing a NEC incidence reduction of up to 0% (p < 0.001). We showed that hBM-MSCs enhanced intestinal cell survival, preserving intestinal barrier integrity and decreasing mucosal inflammation and apoptosis. In conclusion, we established a novel NEC animal model and demonstrated that hBM-MSCs administration reduced the NEC incidence and severity in a concentration-dependent manner, enhancing intestinal barrier integrity.

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