Basic Science PaperStem cells and necrotizing enterocolitis: A direct comparison of the efficacy of multiple types of stem cells
Section snippets
Cell culture
All cell cultures were derived from timed-pregnant Lewis rats (Rat Resource and Research Center, University of Missouri, Columbia, MO), sacrificed at E14.5 of gestation (estimated day 14.5 of an average 22 day gestation).
AF-MSC cells were obtained using modifications of previously described procedures [10], [11]. AF was harvested via 25ga needle aspiration of amniotic sacs. Cells were cultured in Minimum Essential Medium Alpha with GlutaMAX™ (MEM- α, ThermoFisher, Waltham, MA), supplemented with
NEC incidence and severity
No breastfed control pups developed NEC (0%) (Fig. 4). Compared to breastfed pups, 61.3% of pups exposed to experimental stress that received PBS alone developed NEC (p < 0.0001). Compared to pups that received PBS, pups that received SC had the following incidences of NEC: AF-MSC 19.1% (p < 0.0001); BM-MSC 22.9% (p < 0.0001); AF-NSC 18.9% (p < 0.0001); E-NSC 22.2% (p = 0.0002). No significant difference was found between different SC types with respect to ability to decrease experimental NEC.
Discussion
Although recent advances have significantly improved survival of premature infants at younger gestational ages and weights, the morbidity and mortality of NEC remain unacceptably high [26]. Numerous in vivo animal studies have demonstrated success with individual types of stem cells. BM-MSCs and E-NSCs have been shown in multiple studies, including our own, to be effective at reducing experimental NEC [5], [6], [7], [23]. Zani et al. have shown that AF-MSCs are effective in treating
Conclusions
In this study, different types of stem cells (AF-MSC, BM-MSC, AF-NSC, or E-NSC) significantly reduce the incidence and severity of NEC to an equivalent degree. Future use of AF-MSC may be preferable because of the availability of amniotic fluid at delivery and the ease with which AF-derived cells can be cultured. This consideration may be important for future clinical translation.
Acknowledgements
We thank Satoru Otsuru, MD, PhD, in the Center for Childhood Cancer and Blood Diseases at Nationwide Children's Hospital for assistance with culturing of BM-MSC, and Yongjie Miao from the Biostatistics Core of the Research Institute at Nationwide Children's Hospital for assistance with statistical analyses.
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