Publicaciones científicas

Human Bone Marrow-Derived Mesenchymal Stromal Cells Reduce the Severity of Experimental Necrotizing Enterocolitis in a Concentration-Dependent Manner

27-feb-2023 | Revista: Cells

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


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.

CITA DEL ARTÍCULO  Cells. 2023 Feb 27;12(5):760. doi: 10.3390/cells12050760