Stem cells and necrotizing enterocolitis: A direct comparison of the efficacy of multiple types of stem cells

Abstract

Purpose Necrotizing enterocolitis (NEC) is a leading cause of gastrointestinal morbidity and mortality in premature infants. While studies have shown potential for stem cell (SC) therapy in experimental NEC, no study has compared different SC side-by-side. Our purpose was to determine whether one type of SC may more effectively treat NEC than others. Methods Four SC were compared: (1) amniotic fluid-derived mesenchymal SC (AF-MSC); (2) amniotic fluid-derived neural SC (AF-NSC); (3) bone marrow-derived mesenchymal SC (BM-MSC); and (4) neonatal enteric neural SC (E-NSC). Using an established rat model of NEC, pups delivered prematurely received an intraperitoneal injection of SC. Control pups were injected with PBS. Additional controls were breast-fed by surrogates and not subjected to experimental NEC. Intestinal tissue was graded histologically. Results NEC incidence was: PBS, 61.3%; breast-fed unstressed, 0%; AF-MSC, 19.1%; BM-MSC, 22.9%; AF-NSC, 18.9%; E-NSC 22.2%. All groups demonstrated statistical significance (p<0.05) compared to controls, and there was no difference between SC groups. Conclusion All four SC groups reduced the incidence and severity of experimental NEC equivalently. AF-MSC may be preferable due to availability of AF at delivery and ease of expansion, increasing potential for clinical translation.

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

“…6 Cells induced to form adipocytes stained positively using Oil Red O, confirming the presence of lipid droplets, and cells induced to form osteocytes stained positively using Alizarin Red S, indicating calcium deposition in cells induced to form osteocytes (Figure 2). …”

“…1,18 We have previously shown that the four stem cell types investigated in this study equivalently reduce the incidence and severity of NEC from 61% to 19–23%. 6 However, it remains unclear how these stem cells that are from different sources lead to similarly improved outcomes. We have previously demonstrated that different types of stem cells can affect different areas of the intestine, with transplanted NSCs localizing within the myenteric plexus rather than within regions of epithelial origin.…”

“…5 We have recently compared the following four different types of stem cells and shown them to all have equivalent efficacy in decreasing histologic injury during experimental NEC: AF-MSC, amniotic fluid-derived NSC (AF-NSC), BM-MSC, and E-NSC. 6 However, no study has investigated the ability of different types of stem cells to maintain gut barrier function. Our goal in this study was to determine whether different stem cell types vary in their ability to preserve intestinal mucosal integrity during experimental NEC.…”

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

“…Treatment with CBS-knockdown cells resulted in a significantly more severe median score of 5 (IQR 3-6, p=0.0177), as did treatment with CTH-knockdown (6, IQR 4-7, p=0.0008) and MPST-knockdown cells (6,p=0.0071, Figure 4).…”

“…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].…”