Mechanobiology Institute Singapore, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, 117411, Singapore. Neuroscience Academic Clinical Programme, Duke-NUS Medical School, 20 College Road, 169856, Singapore.
Biomed Mater. 2018 Mar 21;13(3):034111. doi: 10.1088/1748-605X/aaaf2b.
Studies of electrical stimulation therapies for the treatment of neurological disorders, such as deep brain stimulation, have almost exclusively been performed using animal-models. However, because animal-models can only approximate human brain disorders, these studies should be supplemented with an in vitro human cell-culture based model to substantiate the results of animal-based studies and further investigate therapeutic benefit in humans. This study presents a novel approach to analyze the effect of electrical stimulation on the neurogenesis of patient-induced pluripotent stem cell (iPSC) derived neural progenitor cell (NPC) lines, in vitro using a 3D graphene scaffold system. The iPSC-derived hNPCs used to demonstrate the system were collected from patients with Rett syndrome, a debilitating neurodevelopmental disorder. The graphene scaffold readily supported both the wild-type and Rett NPCs. Electrical stimulation parameters were optimized to accommodate both wild-type and Rett cells. Increased cell maturation and improvements in cell morphology of the Rett cells was observed after electrical stimulation. The results of the pilot study of electrical stimulation to enhance Rett NPCs neurogenesis were promising and support further investigation of the therapy. Overall, this system provides a valuable tool to study electrical stimulation as a potential therapy for neurological disorders using patient-specific cells.
研究人员对神经疾病的电刺激疗法进行了深入研究，例如脑深部刺激，这些研究几乎都是在动物模型上进行的。然而，由于动物模型只能近似模拟人类的大脑疾病，因此这些研究应该结合体外基于人类细胞培养的模型，以验证动物模型研究的结果，并进一步研究治疗对人类的益处。本研究提出了一种新的方法，使用 3D 石墨烯支架系统，在体外分析电刺激对源自患者诱导多能干细胞（iPSC）的神经祖细胞（NPC）系神经发生的影响。用于证明该系统的 iPSC 衍生的 hNPC 取自雷特综合征患者，雷特综合征是一种使人衰弱的神经发育障碍。石墨烯支架很容易支持野生型和雷特 NPC。优化了电刺激参数以适应野生型和雷特细胞。电刺激后观察到雷特细胞的成熟度增加和细胞形态改善。对电刺激增强雷特 NPC 神经发生的初步研究结果令人鼓舞，支持进一步研究该疗法。总的来说，该系统为使用患者特异性细胞研究电刺激作为神经疾病潜在治疗方法提供了有价值的工具。
