Human Bone Marrow-Derived Mesenchymal Stromal Cells Reduce the Severity of Experimental Necrotizing Enterocolitis in a Concentration-Dependent Manner
Livia Provitera 1 , Andrea Tomaselli 1 2 , Genny Raffaeli 1 2 , Stefania Crippa 3 , Cristina Arribas 4 , Ilaria Amodeo 1 , Silvia Gulden 5 , Giacomo Simeone Amelio 1 , Valeria Cortesi 1 2 , Francesca Manzoni 1 2 , Gaia Cervellini 1 2 , Jacopo Cerasani 1 2 , Camilla Menis 1 2 , Nicola Pesenti 1 6 7 , Matteo Tripodi 1 , Ludovica Santi 3 , Marco Maggioni 8 , Caterina Lonati 9 , Samanta Oldoni 9 , Francesca Algieri 10 , Felipe Garrido 4 , Maria Ester Bernardo 3 11 12 , Fabio Mosca 1 2 , Giacomo Cavallaro 1
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.