Evaluating the efficacy of different types of stem cells in preserving gut barrier function in necrotizing enterocolitis

Abstract

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.

Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis

“…The cost of treating infants with NEC exceeds $1 billion in the US each year [2]. Babies who survive NEC frequently have long term complications including short bowel syndrome, developmental delays and neurological sequelae [1][2][3]. Unfortunately, despite much research over the past decades, a cure has not been identified.…”

“…Previous research has demonstrated that different types of stem cells (SC) have the ability to reduce the incidence and severity of experimental NEC. Furthermore, extracellular vesicles (EVs) derived from SC are similarly protective against NEC, suggesting that they mediate the therapeutic effects of the SC from which they originate [1,2]. EVs are nanovesicles,~20-200 nm in size, that are released by many cells in the body and are ubiquitously present in body fluids including saliva, urine, and breast milk [4].…”

Inhibiting hydrogen sulfide production in umbilical stem cells reduces their protective effects during experimental necrotizing enterocolitis

“…Researchers in the field of experimental NEC have demonstrated that stem cells are beneficial in therapy for this condition [3,5,20,21]. The question remains as to how these cells are workingwhether it is by paracrine effects or by integration into the damaged tissue with regeneration.…”

“…Multiple animal studies have demonstrated improved intestinal architecture with stem cell therapy, often directly injected into the peritoneal cavity [5,6]. Inhibiting the paracrine action of H 2 S in these cells is novel and demonstrates that release of this gasotransmitter is a possible mechanism for intestinal protection.…”

“…Umbilical mesenchymal stem cells (USC) are isolated from the umbilical cord and are considered multipotent [3]. They have been used with success in animal models of ischemia and reperfusion [4] as well as NEC [5,6]. Stem cells are helpful in repairing tissue through multiple mechanisms including migration and engraftment, heterotopic cell fusion, and paracrine effects including exosome release [3].…”