Jagiellonian University Medical College, Faculty of Medicine, Institute of Pediatrics, Department of Transplantation, Wielicka 265, 30-663 Kraków, Poland.
Int J Mol Sci. 2020 Jan 21;21(3):694. doi: 10.3390/ijms21030694.
Organoids are becoming particularly popular in modeling diseases that are difficult to reproduce in animals, due to anatomical differences in the structure of a given organ. Thus, they are a bridge between the in vitro and in vivo models. Human midbrain is one of the structures that is currently being intensively reproduced in organoids for modeling Parkinson's disease (PD). Thanks to three-dimensional (3D) architecture and the use of induced pluripotent stem cells (iPSCs) differentiation into organoids, it has been possible to recapitulate a complicated network of dopaminergic neurons. In this work, we present the first organoid model for an idiopathic form of PD. iPSCs were generated from peripheral blood mononuclear cells of healthy volunteers and patients with the idiopathic form of PD by transduction with Sendai viral vector. iPSCs were differentiated into a large multicellular organoid-like structure. The mature organoids displayed expression of neuronal early and late markers. Interestingly, we observed statistical differences in the expression levels of LIM homeobox transcription factor alpha (early) and tyrosine hydroxylase (late) markers between organoids from PD patient and healthy volunteer. The obtained results show immense potential for the application of 3D human organoids in studying the neurodegenerative disease and modeling cellular interactions within the human brain.
类器官在模拟因特定器官结构的解剖差异而难以在动物中重现的疾病方面变得越来越受欢迎。因此，它们是体外和体内模型之间的桥梁。人类中脑是目前正在类器官中被密集复制以模拟帕金森病（PD）的结构之一。由于 3D 结构和诱导多能干细胞（iPSCs）分化为类器官的使用，已经有可能重现多巴胺能神经元的复杂网络。在这项工作中，我们提出了用于特发性 PD 的首个类器官模型。通过使用 Sendai 病毒载体转导，从健康志愿者和特发性 PD 患者的外周血单核细胞中生成 iPSCs。iPSCs 分化为大型多细胞类器官样结构。成熟的类器官显示出神经元早期和晚期标志物的表达。有趣的是，我们观察到来自 PD 患者和健康志愿者的类器官之间 LIM 同源盒转录因子 alpha（早期）和酪氨酸羟化酶（晚期）标志物的表达水平存在统计学差异。所获得的结果表明 3D 人类类器官在研究神经退行性疾病和模拟人类大脑内细胞相互作用方面具有巨大的应用潜力。
