Transplanted neural crest cells migrate toward Auerbach's plexus layer instead of the colon surface in recipient colon pretreated with collagenase and fibronectin
Transplanted neural crest cells migrate toward Auerbach's plexus layer instead of the colon surface in recipient colon pretreated with collagenase and fibronectin
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在用胶原酶和纤连蛋白预处理的受体结肠中，移植的神经嵴细胞向奥尔巴赫神经丛层迁移，而不是向结肠表面迁移
DOI：
10.1016/j.bbrc.2022.02.094
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发表时间：
2022
影响因子：
3.1
通讯作者：
Okajima Hideaki
中科院分区：
文献类型：
--
作者：
Yasui Yoshitomo;Yoshizaki Hisayoshi;Kuwahara Tsuyoshi;Nishida Shoichi;Kohno Miyuki;Okajima Hideaki
肠神经系统（ENS）调节胃肠运动、分泌和吸收。发育性ENS发育不良引起肠神经节功能障碍，包括先天性巨结肠病。考虑到它们补充不足神经元的潜在能力，肠神经细胞移植提供了治愈的前景。在这项研究中，我们使用离体小鼠结肠移植模型来证明胶原酶和纤维连接蛋白处理改变了移植细胞从结肠表面向管腔方向的迁移。胶原酶处理后的结肠III型和VI型胶原表达增强，抑制了纤维连接蛋白诱导的肠神经嵴细胞（ENCC）迁移。神经球侵入结肠依赖于术前对受体结肠进行胶原酶和纤维连接蛋白处理，增强神经球向结肠管腔方向的运动性。胶原酶处理的结肠以神经球依赖的方式诱导周围平滑肌细胞去分化，而移植的ENCCs在结肠中的浸润程度与周围平滑肌细胞的去分化程度成正比。此外，在处理过的结肠中观察到gdnf表达的诱导，gdnf是一种促进肠内神经细胞迁移的Ret配体。我们的研究结果表明，结肠表面细胞外基质提供的环境影响了移植的ENCC迁移的方向。此外，这些发现表明ENCCs可以被受体结肠接受，这将有助于改进当前的细胞治疗策略。
The enteric nervous system (ENS) regulates gastrointestinal motility, secretion, and absorption. Developmental ENS dysplasia causes intestinal ganglion dysfunction, including Hirschsprung's disease. Given their potential ability to replenish insufficient neurons, transplantation of enteric neural cells provides the prospect of a cure. In this study, we used an ex vivo mouse colon transplant model to demonstrate that treatment with collagenase and fibronectin altered the migration of transplanted cells from the direction of the colon surface toward the lumen. Collagenase-treated colons exhibited enhanced expression of type III and VI collagens, which inhibited fibronectin-induced enteric neural crest cell (ENCC) migration. Invasion of neurospheres into colon was dependent on preoperative treatment of recipient colon with collagenase and fibronectin, which enhanced neurosphere motility towards the direction of colon lumen. Infiltration of transplanted ENCCs into the colon increased proportionally to the degree of dedifferentiation of surrounding smooth muscle cells, which was induced in a neurosphere-dependent manner in collagenase-treated colon. Furthermore, induction ofGDNFexpression, a Ret ligand that promotes enteric neural cell migration, was observed in treated colons. Our results suggest that the environment provided by the extracellular matrix of the colon surface affects the direction of transplanted ENCC migration. Moreover, these findings demonstrating that ENCCs can be accepted by the recipient colon will help to refine current strategies for cell therapy.