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在Hirschsprung病中获得人类ENS血统用于细胞治疗和药物发现

Faranak Fattahi^1,2,3, Julius A Steinbeck^1,2, Sonja Kriks^1,2

¹The Center for Stem Cell Biology, New York, New York 10065, USA.

|February 11, 2016

概括

人类多能干细胞有效地产生肠道神经系统的祖先. 这些细胞可以治疗小鼠的赫斯普隆病,并为研究内脏神经系统发育和潜在疗法提供新的模型.

科学领域:

神经科学
发育生物学
干细胞生物学

背景情况:

肠道神经系统 (ENS) 是"第二大脑",对肠道功能至关重要.
脑内神经元前代迁移的发育缺陷会导致像赫斯普隆病 (HSCR) 这样的疾病.
由于有限的模型系统, 人类内脏神经系统的发育是很难理解的.

研究的目的:

建立基于人类多能干细胞的平台来研究内脏神经系统的发育.
从人类干细胞中产生功能性肠道神经元和原始细胞.
探索基于细胞和药物的HSCR治疗策略.

主要方法:

从人类多能干细胞中提取和分离ENS原始细胞.
在实验室中将原始细胞分化为功能性肠道神经元.
在胚胎和小鼠模型中进行体内迁移和移植研究.

主要成果:

从多能干细胞有效地产生人体内神经元和神经元.
在体外获得的ENS前体在体内显示有针对性的迁移和殖民.
在HSCR小鼠模型中植入人类ENS前体挽救了死亡率.
模拟HSCR迁移缺陷,并确定酸A作为治疗点.

结论:

一个基于人类多能干细胞的新型平台,用于ENS发育研究.
来自干细胞的ENS前体在HSCR治疗中的被证明潜力.
鉴定了酸A作为HSCR的潜在治疗剂.

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