Neurodegenerative disorders have an enormous impact on society and healthcare budgets. There has been a high degree of failure in many recent clinical trials for disease-modifying therapeutics. A major factor in this failure is the difficulty of translating findings from animal-based cell models to human patients. The majority of non-animal neurodegenerative disease research has been conducted in 2 dimensional models of rodent neonatal neurons and glia. While these systems have provided valuable insights into neural cell function and dysfunction, they have largely reached the end of their useful life, as human stem cell technologies combined with major advances in microfluidic technologies have opened the door to development of patient-derived 3D brain cell models. These have major advantages in providing a micro-physiological system more closely reflecting the in vivo brain environment, and promote the interaction between different patient-derived brain cell-types. However, major challenges remain before these model systems will replace the 2D rodent models as the workhorse for neurodegenerative disease studies. Despite these challenges, we are likely to experience a rapid transition of research from old models to new patient derived 3D brain cell systems, which will likely improve translational outcomes for disease therapeutics.

神经退行性疾病对社会和医疗保健预算有巨大影响。在最近的许多疾病改良疗法的临床试验中都存在很大的失败。导致失败的主要因素是难以将基于动物的细胞模型的发现转化为人类患者。大多数非动物神经退行性疾病的研究都是在啮齿动物新生神经元和神经胶质的二维模型中进行的。尽管这些系统为神经细胞功能和功能障碍提供了宝贵的见识，但它们已基本达到使用寿命，因为人类干细胞技术与微流体技术的重大进步为患者衍生的3D脑细胞的发展打开了大门楷模。这些在提供更紧密反映体内脑环境的微生理系统方面具有主要优势，并促进了不同患者来源的脑细胞类型之间的相互作用。然而，在这些模型系统将取代2D啮齿动物模型作为神经退行性疾病研究的主力军之前，仍然存在重大挑战。尽管存在这些挑战，我们仍可能会经历从旧模型到新的患者衍生3D脑细胞系统的快速研究转变，这可能会改善疾病治疗方法的转化结果。