Center for Molecular Medicine, University of Georgia, Athens, GA, USA.
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA, USA.
Clin Auton Res. 2019 Aug;29(4):367-384. doi: 10.1007/s10286-018-00587-4. Epub 2019 Jan 10.
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.
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内稳态至关重要。ANS 的疾病可能由于环境损伤如损伤、毒素/药物和感染或由于遗传损伤而产生。人类研究和动物模型对于理解 ANS 的连接和调节及其疾病至关重要。然而，由于难以大量获得源自人类患者的 ANS 细胞来进行有意义的研究，因此对 ANS 疾病的细胞病理学和分子机制的研究受到了阻碍，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）技术可以巧妙地解决这些问题，允许无限获取源自患者的 ANS 细胞类型进行细胞、分子和生化分析，促进新的治疗靶点的发现，并最终导致药物发现。此外，这些细胞可能为细胞替代疗法提供来源，以补充患者中丢失或受损的 ANS 组织。在这里，我们首先回顾 ANS 的解剖结构和胚胎发育，因为这是理解疾病建模方法的关键。然后，我们回顾用于建模 ANS 疾病的人类干细胞技术的最新进展、细胞替代疗法和药物发现计划的最新进展。
