Rubio Adrian Domene, Hamilton Luke, Bausch Mark, Jin Mengmeng, Papetti Ava, Jiang Peng, Yelamanchili Sowmya V
Department of Anesthesiology, University of Nebraska Medical Center (UNMC), Omaha, NE, 68198, USA.
University of Notre Dame, Notre Dame, IN, 46556, USA.
J Neuroimmune Pharmacol. 2025 Feb 22;20(1):23. doi: 10.1007/s11481-025-10181-x.
Most current information about neurological disorders and diseases is derived from direct patient and animal studies. However, patient studies in many cases do not allow replication of the early stages of the disease and, therefore, offer limited opportunities to understand disease progression. On the other hand, although the use of animal models allows us to study the mechanisms of the disease, they present significant limitations in developing drugs for humans. Recently, 3D-cultured in vitro models derived from human pluripotent stem cells have surfaced as a promising system. They offer the potential to connect findings from patient studies with those from animal models. In this comprehensive review, we discuss their application in modeling neurodevelopmental conditions such as Down Syndrome or Autism, neurodegenerative diseases such as Alzheimer's or Parkinson's, and viral diseases like Zika virus or HIV. Furthermore, we will discuss the different models used to study prenatal exposure to drugs of abuse, as well as the limitations and challenges that must be met to transform the landscape of research on human brain disorders.
目前,关于神经紊乱和疾病的大多数信息都来自对患者和动物的直接研究。然而,在许多情况下,患者研究无法重现疾病的早期阶段,因此,了解疾病进展的机会有限。另一方面,尽管使用动物模型使我们能够研究疾病的机制,但在开发用于人类的药物方面,它们存在重大局限性。最近,源自人类多能干细胞的三维体外培养模型已成为一个很有前景的系统。它们有可能将患者研究的结果与动物模型的结果联系起来。在这篇全面综述中,我们讨论了它们在模拟神经发育疾病(如唐氏综合征或自闭症)、神经退行性疾病(如阿尔茨海默病或帕金森病)以及病毒性疾病(如寨卡病毒或艾滋病毒)方面的应用。此外,我们还将讨论用于研究产前接触滥用药物的不同模型,以及改变人类脑部疾病研究格局必须克服的局限性和挑战。