1 research outputs found
Human bone marrow-derived mesenchymal stromal cells reduce the severity of experimental necrotizing enterocolitis in a concentration-dependent manner
: 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