Enhancement of enteric neural stem cell neurogenesis by glial cell-derived neurotrophic factor in experimental Hirschsprung's disease.

IF 1.5 3区医学 Q2 PEDIATRICS

Pediatric Surgery International Pub Date : 2024-10-26 DOI:10.1007/s00383-024-05861-3

Naho Fujiwara, Dorothy Lee, Bo Li, Agostino Pierro, Atsuyuki Yamataka

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引用次数: 0

Abstract

Purpose: Stem cell therapy offers a promising solution for congenital diseases like Hirschsprung's disease (HSCR). Optimizing stem cell efficacy by modifying the cells and their environment is crucial, but in vitro culture conditions need to be further improved. Glial cell-derived neurotrophic factor (GDNF) plays an important role in neuronal survival, proliferation, migration and differentiation during enteric nervous system (ENS) development. In this study, the effects of GDNF on neurites derived from an Ednrb knockout model were investigated with the aim of enhancing the neurogenic potential of enteric neural crest cells (ENCCs).

Methods: Neurospheres were generated form Ednrb^+/+ (control) and Ednrb^-/- mice at embryonic day13.5 (E13.5) with Sox10-green fluorescent protein (Venus) transgenic expression. These neurospheres were cultured in control media and neurospheres from Ednrb^-/- were cultured with either control media or media supplemented with GDNF. ENCCs differentiation was assessed using immunofluorescence staining after 18 days.

Results: GDNF-treated Ednrb^-/- neurospheres showed increased size and higher density of Sox10-positive ENCCs compared to untreated Ednrb^-/- neurospheres. GDNF also enhanced the distribution of both TUJ1-positive neurons and S100-positive glial cells.

Conclusion: GDNF effectively enhanced the neurogenic potential of ENCCs from HSCR animal model. This finding is crucial for the development of cell therapy in HSCR.

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胶质细胞源性神经营养因子在实验性赫氏胃肠病中增强肠道神经干细胞的神经发生。

目的：干细胞疗法为治疗先天性疾病（如赫氏贲门失弛缓症）提供了一种前景广阔的解决方案。通过改变细胞及其环境来优化干细胞疗效至关重要，但体外培养条件需要进一步改善。胶质细胞源性神经营养因子（GDNF）在肠道神经系统（ENS）发育过程中的神经元存活、增殖、迁移和分化中发挥着重要作用。本研究调查了 GDNF 对来自 Ednrb 基因敲除模型的神经元的影响，旨在增强肠神经嵴细胞（ENCCs）的神经源潜能：在胚胎第13.5天（E13.5），用Sox10-绿色荧光蛋白（Venus）转基因表达的Ednrb+/+（对照组）和Ednrb-/-小鼠产生神经球。这些神经球在对照培养基中培养，而 Ednrb-/- 的神经球则在对照培养基或添加 GDNF 的培养基中培养。18天后用免疫荧光染色法评估ENCCs的分化情况：结果：与未经处理的Ednrb-/-神经球相比，经GDNF处理的Ednrb-/-神经球显示出更大的尺寸和更高密度的Sox10阳性ENCCs。GDNF还增强了TUJ1阳性神经元和S100阳性神经胶质细胞的分布：结论：GDNF能有效增强HSCR动物模型ENCCs的神经源潜能。结论：GDNF 能有效增强 HSCR 动物模型 ENCCs 的神经源潜能，这一发现对开发 HSCR 细胞疗法至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric Surgery International 医学-外科

CiteScore

3.00

自引率

5.60%

发文量

215

审稿时长

3-6 weeks

期刊介绍： Pediatric Surgery International is a journal devoted to the publication of new and important information from the entire spectrum of pediatric surgery. The major purpose of the journal is to promote postgraduate training and further education in the surgery of infants and children. The contents will include articles in clinical and experimental surgery, as well as related fields. One section of each issue is devoted to a special topic, with invited contributions from recognized authorities. Other sections will include: -Review articles- Original articles- Technical innovations- Letters to the editor