Induced pluripotent stem cells for disease modeling, cell therapy and drug discovery in genetic autonomic disorders: a review.

Kenyi Saito-Diaz, Nadja Zeltner
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引用次数: 12

Abstract

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.

诱导多能干细胞在遗传性自主神经疾病中的疾病建模、细胞治疗和药物发现:综述。
自主神经系统(autonomic nervous system, ANS)独立于意识调节身体的所有器官,因此对维持整个生物体的内稳态至关重要。非裔美国人的疾病可能由于环境的损害,如伤害、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有助于理解ANS及其疾病的连通性和调控。然而,由于难以获得大量人类患者来源的ANS细胞进行有意义的研究,阻碍了对ANS疾病的细胞病理学和分子机制的研究,主要原因是患者神经元不容易活检,人类原代神经元培养不能扩大。人类诱导多能干细胞(hiPSC)技术可以很好地解决这些问题,允许无限制地使用患者来源的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,并最终导致药物的发现。此外,这些细胞可能为细胞替代疗法提供来源,以补充患者丢失或受伤的ANS组织。在这里,我们首先回顾了ANS的解剖和胚胎发育,因为这些知识对于理解疾病建模方法至关重要。然后,我们回顾了目前人类干细胞技术在模拟ANS疾病方面的进展,最近在细胞替代疗法和药物发现方面的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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