Background
Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in premature infants. Increased intestinal permeability is central to NEC development. We have shown that stem cells (SC) can reduce the incidence and severity of NEC. Our current goal was to investigate the efficacy of four different types of SC in preservation of gut barrier function during NEC.
Materials and Methods
We compared: (1) amniotic fluid-derived mesenchymal SC (AF-MSC); (2) bone marrow-derived MSC (BM-MSC); (3) amniotic fluid-derived neural SC (AF-NSC); and (4) enteric NSC (E-NSC). Premature rat pups received an intraperitoneal injection of 2×106 SC or PBS only, and were then subjected to experimental NEC. Control pups were breastfed and not subjected to NEC. After 48h animals received a single enteral dose of FITC-labeled dextran (FD70), were sacrificed 4h later, and serum FD70 concentrations determined.
Results
Compared to breastfed, unstressed pups with intact gut barrier function and normal intestinal permeability (serum FD70 concentration 2.22 ± 0.271 μg/mL), untreated pups exposed to NEC had impaired barrier function with significantly increased permeability (18.6 ± 4.25 μg/mL, p=0.047). Pups exposed to NEC but treated with SC had significantly reduced intestinal permeability: AF-MSC (9.45 ± 1.36 μg/mL, p=0.017); BM-MSC (6.73 ±2.74 μg/mL, p=0.049); AF-NSC (8.052 ± 1.31 μg/mL, p=0.0496); and E-NSC (6.60 ± 1.46 μg/mL, p=0.033).
Conclusions
Stem cells improve gut barrier function in experimental NEC. Although all four types of SC reduce permeability equivalently, SC derived from amniotic fluid may be preferable due to availability at delivery and ease of culture, potentially enhancing clinical translation.
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