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 marr...

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Autores: Provitera, L. (Livia)|||/items/6424e06c-ae79-4968-8517-b32e7bc31126, Tomaselli, A. (Andrea)|||/items/70c2cb25-e3b1-4ac2-8a97-acd82a2c2bb7, Raffaeli, G. (Genny)|||/items/87f5b2e0-2104-4645-a3d7-f0af997957ff, Crippa, S. (Stefania)|||/items/d2b93b20-b518-4904-9ba9-f3c298089299, Arribas-Sánchez, C. (Cristina)|||/items/794362d2-48bd-439b-94b6-e0ca3791f145, Amodeo, I. (Ilaria)|||/items/024e7b2d-660e-46d9-ad9a-2d2ea6445883, Gulden, S. (Silvia)|||/items/6f323574-6d9b-4370-bc0d-e4a71c970990, Amelio, G.S. (Giacomo Simeone)|||/items/dfaad7b2-7d1c-47ec-9f4f-87a353896159, Cortesi, V. (Valeria)|||/items/1c839b8e-4c97-40a7-be3b-58cc6d95867e, Manzoni, F. (Francesca)|||/items/b262d6ed-26f5-4277-b956-dc7d8e51b1e6, Cervellini, G. (Gaia)|||/items/4b9a80bd-3bf6-4e3d-9eac-6bf9b527dd14, Cerasani, J. (Jacopo)|||/items/0fad45e2-14f7-42ea-b35d-55496e35903d, Menis, C. (Camilla)|||/items/08ee50df-ff10-4596-83a6-3643ce8e8f77, Pesenti, N. (Nicola)|||/items/b91b6cdc-ee83-4e86-a440-52d1bd128ed8, Tripodi, M. (Matteo)|||/items/f3e15dfe-8e18-4080-aab4-57790032e3b5, Santi, L. (Ludovica)|||/items/97a6dbce-1272-4cb8-b816-84ec41f696cb, Maggioni, M. (Marco)|||/items/7a7e3cd5-a655-481d-b3f1-967265428d6f, Lonati, C. (Caterina)|||/items/d968aaad-ab49-4e8f-b9a6-4f4dd153c22b, Oldoni, S. (Samanta)|||/items/8a165eed-da87-44c8-a752-7e15fbd2bda1, Algieri, F. (Francesca)|||/items/20de306f-ba6f-424b-8a2e-726b696fbf01, Garrido-Martínez-de-Salazar, F. (Felipe)|||/items/40beaf89-1e51-40c9-b02a-01725e3f4d51, Bernardo, M.E. (Maria Ester)|||/items/08a6fc9d-239b-4cd9-8d10-dc4122190d86, Mosca, F. (Fabio)|||/items/6466c471-4d37-43dd-a48b-0a3ff3e34a46, Cavallaro, G. (Giacomo)|||/items/8063b6c8-3615-4530-a5b8-558b69b5d428
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/68356
Acceso en línea:https://hdl.handle.net/10171/68356
Access Level:acceso abierto
Palabra clave: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
Descripción
Sumario:: 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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