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基于小鼠实验性坏死性小肠结肠炎模型探讨干细胞在疾病预防中的潜在作用。

Potential role of stem cells in disease prevention based on a murine model of experimental necrotizing enterocolitis.

作者信息

Pisano Courtney, Besner Gail E

机构信息

Department of Pediatric Surgery, Center for Perinatal Research, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH, 43205, USA.

Department of Pediatric Surgery, Center for Perinatal Research, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH, 43205, USA.

出版信息

J Pediatr Surg. 2019 Mar;54(3):413-416. doi: 10.1016/j.jpedsurg.2018.07.025. Epub 2018 Sep 5.

DOI:10.1016/j.jpedsurg.2018.07.025
PMID:30236604
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6380911/
Abstract

BACKGROUND

Necrotizing enterocolitis (NEC) is a devastating disease of newborns, and despite years of research, there is no known cure. The mortality rate of infants with NEC remains as high as 20%-30%. Babies who survive NEC frequently have long term complications including short gut syndrome, developmental delays and neurological sequelae. Unfortunately, despite much research over the past years, the precise pathogenesis of the disease is still not completely understood.

METHODS

Our laboratory has focused on identifying novel therapies to prevent the disease, including the use of stem cells (SC), heparin-binding epidermal growth factor-like growth factor (HB-EGF) and recently, stem cell derived-exosomes, a type of nanovesicle, to combat this illness.

RESULTS

We have outlined the major SC lines and data suggesting potential benefit as a curative or preventive approach for NEC as well as describing several new therapeutic strategies, including stem cell derived- exosomes and HB-EGF for decreasing the incidence and severity of this disease in rat models in our lab.

CONCLUSION

Overall, our lab has demonstrated that these different types of SC equivalently reduce the incidence and severity of NEC and equally preserve intestinal barrier function during NEC. We have previously demonstrated that AF-MSC can protect the intestines from intestinal injury and may therefore hold strong therapeutic potential for the prevention of NEC. Most recently, our work with stem cell derived-exosomes has shown them to be equivalent to their derived SC lines in decreasing the incidence of this disease.

摘要

背景

坏死性小肠结肠炎(NEC)是一种严重的新生儿疾病,尽管经过多年研究,仍无已知的治愈方法。NEC婴儿的死亡率仍高达20%-30%。NEC存活的婴儿经常有长期并发症,包括短肠综合征、发育迟缓及神经后遗症。不幸的是,尽管过去几年进行了大量研究,但该疾病的确切发病机制仍未完全明了。

方法

我们实验室专注于确定预防该疾病的新疗法,包括使用干细胞(SC)、肝素结合表皮生长因子样生长因子(HB-EGF),以及最近使用干细胞衍生的外泌体(一种纳米囊泡)来对抗这种疾病。

结果

我们概述了主要的干细胞系以及表明其作为NEC治疗或预防方法具有潜在益处的数据,还描述了几种新的治疗策略,包括在我们实验室的大鼠模型中使用干细胞衍生的外泌体和HB-EGF来降低该疾病的发病率和严重程度。

结论

总体而言,我们实验室已证明,这些不同类型的干细胞同等程度地降低了NEC的发病率和严重程度,并在NEC期间同样保护肠道屏障功能。我们之前已证明羊膜间充质干细胞可以保护肠道免受肠损伤,因此可能对预防NEC具有强大的治疗潜力。最近,我们对干细胞衍生外泌体的研究表明,它们在降低该疾病发病率方面与它们所衍生的干细胞系等效。

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J Pediatr Surg. 2018 Jun;53(6):1215-1220. doi: 10.1016/j.jpedsurg.2018.02.086. Epub 2018 Mar 14.
2
Stem cell therapy in necrotizing enterocolitis: Current state and future directions.坏死性小肠结肠炎的干细胞治疗:现状与未来方向。
Semin Pediatr Surg. 2018 Feb;27(1):57-64. doi: 10.1053/j.sempedsurg.2017.11.011. Epub 2017 Nov 7.
3
Evaluating the efficacy of different types of stem cells in preserving gut barrier function in necrotizing enterocolitis.评估不同类型干细胞在坏死性小肠结肠炎中维持肠道屏障功能的疗效。
J Surg Res. 2017 Jun 15;214:278-285. doi: 10.1016/j.jss.2017.03.026. Epub 2017 Mar 31.
4
Stem cells and necrotizing enterocolitis: A direct comparison of the efficacy of multiple types of stem cells.干细胞与坏死性小肠结肠炎:多种类型干细胞疗效的直接比较
J Pediatr Surg. 2017 Jun;52(6):999-1005. doi: 10.1016/j.jpedsurg.2017.03.028. Epub 2017 Mar 18.
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Emerging potential of exosomes for treatment of traumatic brain injury.外泌体治疗创伤性脑损伤的新潜力。
Neural Regen Res. 2017 Jan;12(1):19-22. doi: 10.4103/1673-5374.198966.
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Differences in the Clinical Characteristics of Early- and Late-Onset Necrotizing Enterocolitis in Full-Term Infants: A Retrospective Case-Control Study.足月新生儿早发性和晚发性坏死性小肠结肠炎临床特征的差异:一项回顾性病例对照研究。
Sci Rep. 2017 Feb 17;7:43042. doi: 10.1038/srep43042.
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A new approach in stem cell research-Exosomes: Their mechanism of action via cellular pathways.干细胞研究的一种新方法——外泌体:其通过细胞途径的作用机制。
Cell Biol Int. 2017 May;41(5):466-475. doi: 10.1002/cbin.10742. Epub 2017 Mar 31.
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Mesenchymal Stem Cell-Derived Extracellular Vesicles as Mediators of Anti-Inflammatory Effects: Endorsement of Macrophage Polarization.间质干细胞衍生的细胞外囊泡作为抗炎作用的介质:促进巨噬细胞极化。
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Charge-based precipitation of extracellular vesicles.基于电荷的细胞外囊泡沉淀
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