Development and Use of a Tissue and Human Enteroid Biorepository to Study the Pathophysiology of NEC

Development and Use of a Tissue and Human Enteroid Biorepository to Study the Pathophysiology of Neonatal Necrotizing Enterocolitis

Despite a greater understanding of NEC physiopathology, modest progress has been done in terms of intervention and prevention of the disease over the past three decades, being the mortality rate unchanged.

Investigators intend to leverage our knowledge and technical expertise developed with fetal enteroids to further investigate the processes leading to NEC by deriving and performing functional studies on human intestinal enteroids generated from intestinal resection for therapeutic reasons in NEC and non-NEC patients

1. Generate a tissue biorepository composed of: enteroids and other lamina propria cells
2. Comparative studies of the gene expression profile of tissue, epithelial enteroids and underlying lamina propria of NEC, non-NEC, hypoxic and non-hypoxic infants
3. In vitro functional studies for the evaluation of critical factors in NEC pathophysiology
4. In vitro functional studies to identify the activation of processes leading to intestinal epithelium necroptosis and/or apoptosis in bacteria challenged and hypoxic conditions
5. Correlative studies of the impact of perinatal variables on the intestinal barrier functionality at baseline and challenged with pathogens
6. In vitro comparison of the intestinal barrier functionality in infants complicated by condition of prenatal hypoxia versus non hypoxic infants
7. Validation the NEC enteroids as an in vitro model for the identification of treatments and prevention of NEC

Inclusion Criteria:

• Infants, with a postconceptional age below 44 weeks of gestation, undergoing a clinically indicated intervention of partial intestinal resection while hospitalized at the NICU of the Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico.

Exclusion Criteria:

• Infants presenting a devastating damage of the intestine