Nickels Sarah Louise, Modamio Jennifer, Mendes-Pinheiro Bárbara, Monzel Anna Sophia, Betsou Fay, Schwamborn Jens Christian
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg; Integrated Biobank of Luxembourg (IBBL), Luxembourg Institute of Health, L-3555 Dudelange, Luxembourg.
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, L-4367 Belvaux, Luxembourg.
Stem Cell Res. 2020 Jul;46:101870. doi: 10.1016/j.scr.2020.101870. Epub 2020 Jun 6.
The study of human midbrain development and midbrain related diseases, like Parkinson's disease (PD), is limited by deficiencies in the currently available and validated laboratory models. Three dimensional midbrain organoids represent an innovative strategy to recapitulate some aspects of the complexity and physiology of the human midbrain. Nevertheless, also these novel organoid models exhibit some inherent weaknesses, including the presence of a necrotic core and batch-to-batch variability. Here we describe an optimized approach for the standardized generation of midbrain organoids that addresses these limitations, while maintaining key features of midbrain development like dopaminergic neuron and astrocyte differentiation. Moreover, we have established a novel time-efficient, fit for purpose analysis pipeline and provided proof of concept for its usage by investigating toxin induced PD.
人类中脑发育及与中脑相关疾病（如帕金森病，PD）的研究受到当前可用且经过验证的实验室模型缺陷的限制。三维中脑类器官是一种创新策略，可概括人类中脑复杂性和生理学的某些方面。然而，这些新型类器官模型也存在一些固有弱点，包括坏死核心的存在和批次间的变异性。在此，我们描述了一种优化方法，用于标准化生成中脑类器官，该方法解决了这些局限性，同时保留了中脑发育的关键特征，如多巴胺能神经元和星形胶质细胞分化。此外，我们建立了一种新型的省时、适用的分析流程，并通过研究毒素诱导的帕金森病为其应用提供了概念验证。
