Postnatal human enteric neuronal progenitors can migrate, differentiate, and proliferate in embryonic and postnatal aganglionic gut environments
Postnatal human enteric neuronal progenitors can migrate, differentiate, and proliferate in embryonic and postnatal aganglionic gut environments
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DOI：
10.1038/pr.2017.4
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发表时间：
2017-05-01
影响因子：
3.6
通讯作者：
Goldstein, Allan M.
中科院分区：
文献类型：
--
作者：
Cheng, Lily S.;Hotta, Ryo;Goldstein, Allan M.
背景：肠神经干/祖细胞（ENSCs）提供了一种治疗先天性巨结肠病（HSCR）和其他肠神经病变的创新方法。然而，出生后衍生的人类ENSCs尚未被完全表征，它们在胚胎和出生后肠道环境中的行为也是未知的。方法：从25例接受肠切除术的患者肠道中分离ENSCs，其中包括7例HSCR患儿。观察了HSCR患者和非HSCR患者粘膜下和肌丛ENSCs的神经元分化和增殖情况。研究了胚胎干细胞移植到胚鸡神经嵴、胚鸡后肠和出生后小鼠神经节结肠后的迁移和分化。结果：来自HSCR肠道的ENSCs的增殖和神经源性潜力与非HSCR对照组相当。同样，在肌肠源性和粘膜下源性ENSCs之间也没有观察到差异。出生后ENSCs移植到胚胎神经嵴通路和神经后肠可正常迁移并分化为合适的神经嵴来源细胞类型。出生后小鼠神经节结肠ENSCs在体外和体内均可分化为神经元和胶质细胞。结论：从HSCR患者和非HSCR患者的出生后肠中分离的ENSCs可以表现出与胚胎神经嵴来源细胞相似的行为。这些结果支持了细胞的可行性
BACKGROUND: Enteric neural stem/progenitor cells (ENSCs) offer an innovative approach to treating Hirschsprung disease (HSCR) and other enteric neuropathies. However, postnatal derived human ENSCs have not been thoroughly characterized and their behavior in the embryonic and postnatal intestinal environment is unknown.METHODS: ENSCs were isolated from the intestines of 25 patients undergoing bowel resection, including 7 children with HSCR. Neuronal differentiation and proliferation of ENSCs from submucosal and myenteric plexuses from patients with and without HSCR were characterized. ENSC migration and differentiation were studied following transplantation into embryonic chick neural crest, embryonic chick hindgut, and postnatal mouse aganglionic colon.RESULTS:The proliferative and neurogenic potential of ENSCs from HSCR intestine is equivalent to that of non-HSCR controls. Similarly, no difference was observed between myenteric- and submucosal-derived ENSCs. Postnatal ENSCs transplanted to embryonic neural crest pathways and to aneural hindgut migrate normally and differentiate into appropriate neural crest-derived cell types. ENSCs in postnatal mouse aganglionic colon differentiate into neurons and glia both ex vivo and in vivo.CONCLUSIONS: ENSCs isolated from the postnatal intestine of patients with and without HSCR can behave like embryonic neural crest-derived cells. These results support the feasibility of cell