自主神经系统(ANS)独立于意识调节身体的所有器官,因此对于维持整个生物体的体内平衡至关重要。ANS的疾病可能是由于诸如伤害之类的环境损害而引起的,毒素/药物和感染或由于遗传病变。人类研究和动物模型有助于理解ANS及其疾病的连接和调节。然而,对ANS疾病的细胞病理学和分子机制的研究由于难以大量获取人类患者来源的ANS细胞进行有意义的研究而受到阻碍,主要是因为患者神经元不容易进行活检,并且原代人神经元培养物不能扩增。人类诱导多能干细胞(hiPSC)技术可以优雅地弥合这些问题,允许无限制地访问患者来源的ANS细胞类型的细胞,分子和生化分析,促进发现新的治疗靶点,最终导致药物发现。此外,这些细胞可以为细胞替代疗法提供来源,以补充患者丢失或受损的ANS组织。这里,我们首先回顾了ANS的解剖结构和胚胎发育,因为这些知识对于理解疾病建模方法至关重要。然后,我们回顾了人类干细胞技术在模拟ANS疾病方面的最新进展,最近向细胞替代疗法和药物发现计划迈进。
The autonomic nervous system (ANS) regulates all organs in the body independent of consciousness, and is thus essential for maintaining homeostasis of the entire organism. Diseases of the ANS can arise due to environmental insults such as injury, toxins/drugs and infections or due to genetic lesions. Human studies and animal models have been instrumental to understanding connectivity and regulation of the ANS and its disorders. However, research into cellular pathologies and molecular mechanisms of ANS disorders has been hampered by the difficulties in accessing human patient-derived ANS cells in large numbers to conduct meaningful research, mainly because patient neurons cannot be easily biopsied and primary human neuronal cultures cannot be expanded.Human-induced pluripotent stem cell (hiPSC) technology can elegantly bridge these issues, allowing unlimited access of patient-derived ANS cell types for cellular, molecular and biochemical analysis, facilitating the discovery of novel therapeutic targets, and eventually leading to drug discovery. Additionally, such cells may provide a source for cell replacement therapy to replenish lost or injured ANS tissue in patients.Here, we first
review the anatomy and embryonic development of the ANS, as this knowledge is crucial for understanding disease modeling approaches. We then
review the current advances in human stem cell technology for modeling diseases of the ANS, recent strides toward cell replacement therapy and drug discovery initiatives.