Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK; Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Translational Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Trends Immunol. 2024 Oct;45(10):799-813. doi: 10.1016/j.it.2024.08.004. Epub 2024 Sep 21.
The importance of neuroinflammation in neurodegenerative diseases is becoming increasingly evident, and, in parallel, human induced pluripotent stem cell (hiPSC) models of physiology and pathology are emerging. Here, we review new advancements in the differentiation of hiPSCs into glial, neural, and blood-brain barrier (BBB) cell types, and the integration of these cells into complex organoids and chimeras. These advancements are relevant for modeling neuroinflammation in the context of prevalent neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). With awareness of current limitations, recent progress in the development and application of various hiPSC-derived models shows potential for aiding the identification of candidate therapeutic targets and immunotherapy approaches.
神经炎症在神经退行性疾病中的重要性日益明显,与此同时,人类诱导多能干细胞(hiPSC)的生理和病理模型也在不断涌现。在这里,我们综述了 hiPSC 向神经胶质细胞、神经元和血脑屏障(BBB)细胞分化的新进展,以及这些细胞整合到复杂类器官和嵌合体中的进展。这些进展对于在常见神经退行性疾病(如阿尔茨海默病(AD)、帕金森病(PD)和多发性硬化症(MS))的背景下模拟神经炎症具有重要意义。考虑到当前的局限性,各种 hiPSC 衍生模型的开发和应用的最新进展显示出有助于确定候选治疗靶点和免疫治疗方法的潜力。