Increased enteric neural crest cell differentiation after transplantation into aganglionic mouse gut
Increased enteric neural crest cell differentiation after transplantation into aganglionic mouse gut
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移植到无神经节小鼠肠道后肠神经嵴细胞分化增加
DOI：
10.1007/s00383-022-05324-7
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发表时间：
2022
期刊：
影响因子：
1.8
通讯作者：
Yamataka A.
中科院分区：
文献类型：
--
作者：
Nakazawa-Tanaka N;Fujiwara N;Miyahara K;Akazawa C;Urao M;Yamataka A.
目的近年来，以干细胞为基础的治疗先天性巨结肠的研究取得了长足的进展。然而，肠神经嵴衍生细胞（ENCC）移植到无神经节肠是否可以正常迁移，增殖和分化的问题仍然没有答案。因此，我们设计了这项研究，比较的行为ENCCs移植到无神经节肠内皮素受体B敲除（Ednrb-KO）小鼠与野生型（WT）mice.MethodsENCCs分离Sox 10转基因小鼠，其中ENCCs被标记的增强绿色荧光蛋白，金星，在胚胎第18.5天（E18.5）的胎儿肠道。在E12.5，产生神经球并移植到Ednrb-KO小鼠肠道或尚未定殖的WT小鼠肠道的无神经节区。在培养24、48和72小时后对移植的ENCC进行延时成像。采用整体免疫组织化学方法评价神经元分化。结果Sox 10阳性ENCC移植到Ednrb-KO和WT小鼠后均成功迁移到无神经节肠的肌间区。与Ednrb-KO小鼠中的24 h相比，在培养72 h后Tuj 1阳性/Sox 10阳性细胞的比率显著增加，这表明移植的ENCC随时间分化。此外，在72小时的时间点，神经元分化的移植ENCC在无神经节肠ofEdnrb-KO小鼠相比，WT mice.ConclusionsThe结果表明，移植ENCC迁移到肌间区的无神经节受体肠小鼠。Endrb-KO小鼠肠内移植ENCC的神经元分化增加表明该区域的微环境影响移植后ENCC的行为。探索这种微环境特征的进一步研究将提高开发细胞疗法治疗HD患者的潜力。
PurposeIn recent years, many studies have made considerable progress in the development of stem cell-based therapies for Hirschsprung’s disease (HD). However, the question of whether enteric neural crest-derived cells (ENCCs) that are transplanted into the aganglionic gut can migrate, proliferate, and differentiate in a normal manner remains unanswered. Thus, we designed this study to compare the behavior of ENCCs transplanted into the aganglionic gut of endothelin receptor B knockout (Ednrb-KO) mice versus wild-type (WT) mice.MethodsENCCs were isolated from the fetal guts of Sox10 transgenic mice, in which ENCCs were labeled with an enhanced green fluorescent protein, Venus, on an embryonic day 18.5 (E18.5). Neurospheres were generated and transplanted into the aganglionic region of eitherEdnrb-KO mice gut, or WT mice gut that had not yet been colonized, on E12.5. Time-lapse imaging of the transplanted ENCCs was performed after 24, 48, and 72 h of culture. Neuronal differentiation was evaluated using whole-mount immunohistochemistry.ResultsSox10-positive ENCCs were seen to successfully migrate into the myenteric region of the aganglionic gut following transplantation in both theEdnrb-KO and WT mice. The ratio of Tuj1-positive/Sox10-positive cells was significantly increased after 72 h of culture compared to 24 h in theEdnrb-KO mice, which suggests that the transplanted ENCCs differentiated over time. In addition, at the 72 h timepoint, neuronal differentiation of transplanted ENCC in the aganglionic gut ofEdnrb-KO mice was significantly increased compared to that of WT mice.ConclusionsThe results of our study demonstrated that transplanted ENCCs migrated into the myenteric region of the aganglionic recipient gut in mice. The increased neuronal differentiation of transplanted ENCC inEndrb-KO mice gut suggests that the microenvironment of this region affects ENCC behavior following transplantation. Further research to explore the characteristics of this microenvironment will improve the potential of developing cell therapy to treat HD patients.
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影响因子：
3.6
作者：
Shibata S;Yasuda A;Renault-Mihara F;Suyama S;Katoh H;Inoue T;Inoue YU;Nagoshi N;Sato M;Nakamura M;Akazawa C;Okano H
通讯作者：
Okano H
影响因子：
2.7
作者：
Nagy, N;Goldstein, AM
通讯作者：
Goldstein, AM
在内皮素受体 B 缺失小鼠模型中，降低肠神经嵴细胞中 β1 整合素的表达。
DOI：
--
发表时间：
2019
期刊：
影响因子：
--
作者：
Nana Nakazawa-Tanaka;Katsumi Miyahara;Naho Fujiwara;Takanori Ochi;Ryo Sueyoshi;Shuko Nojiri;Chihiro Akazawa;Masahiko Urao;Atsuyuki Yamataka
通讯作者：
Atsuyuki Yamataka
肠神经嵴细胞中缺乏 (cid:3) 1 整合素会导致先天性巨结肠表型
DOI：
--
发表时间：
--
期刊：
影响因子：
--
作者：
G. Melkonian;J. L. Wang;J. Chung;N. Munoz;P. Talbot
通讯作者：
P. Talbot
先天性巨结肠中细胞外基质蛋白层粘连蛋白的定量和定性分析。
影响因子：
2.4
作者：
D. Parikh;P. Tam;D. Lloyd;D. van Velzen;D. Edgar
通讯作者：
D. Edgar