Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
Sanford Consortium for Regenerative Medicine, La Jolla, California, USA.
Stem Cells Dev. 2020 Sep 1;29(17):1131-1141. doi: 10.1089/scd.2019.0217. Epub 2020 May 6.
Human neurological disorders are among the most challenging areas of translational research. The difficulty of acquiring human neural samples or specific representative animal models has necessitated a multifaceted approach to understanding disease pathology and drug discovery. The dedifferentiation of somatic cells to human induced pluripotent stem cells (hiPSCs) for the generation of neural derivatives has broadened the capability of biomedical research to study human cell types in neurological disorders. The initial zeal for the potential of hiPSCs for immediate biomedical breakthroughs has evolved to more reasonable expectations. Over the past decade, hiPSC technology has demonstrated the capacity to successfully establish "disease in a dish" models of complex neurological disorders and to identify possible novel therapeutics. However, as hiPSCs are used more broadly, an increased understanding of the limitations of hiPSC studies is becoming more evident. In this study, we review the challenges of studying neurological disorders, the current limitations of stem cell-based disease modeling, and the degrees to which hiPSC studies to date have demonstrated the capacity to fill essential gaps in neurological research.
人类神经紊乱是转化研究中最具挑战性的领域之一。由于难以获取人类神经样本或特定的代表性动物模型，因此需要采用多方面的方法来了解疾病病理学和药物发现。体细胞去分化为人类诱导多能干细胞（hiPSCs）以产生神经衍生物，拓宽了生物医学研究在神经紊乱中研究人类细胞类型的能力。hiPSCs 即刻带来生物医学突破的最初热情已经演变为更合理的期望。在过去的十年中，hiPSC 技术已经证明了成功建立复杂神经紊乱“疾病在培养皿中”模型并确定可能的新型治疗方法的能力。然而，随着 hiPSCs 的更广泛应用，人们越来越清楚地认识到 hiPSC 研究的局限性。在本研究中，我们回顾了研究神经紊乱的挑战、基于干细胞的疾病建模的当前局限性，以及迄今为止 hiPSC 研究在多大程度上填补了神经科学研究中的重要空白。
