Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays and single-cell gene expression analyses reveal that low-intensity ultrasound improves the neural development in cortical organoids. Following organoid grafts transplantation into the injured somatosensory cortices of adult mice, longitudinal electrophysiological recordings and histological assays reveal that ultrasound-treated organoid grafts undergo advanced maturation. They also exhibit enhanced pain-related gamma-band activity and more disseminated projections into the host brain than the untreated groups. Finally, low-intensity ultrasound ameliorates neuropathological deficits in a microcephaly brain organoid model. Hence, low-intensity ultrasound stimulation advances the development and integration of brain organoids, providing a strategy for treating neurodevelopmental disorders and repairing cortical damage.

中文翻译：

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低强度超声改善大脑类器官整合并挽救小头畸形缺陷

人脑类器官代表了神经系统疾病建模的卓越平台和有前途的大脑修复方法。然而，物理刺激对其发育和整合的影响仍不清楚。在这里，我们报告低强度超声显着增加皮质类器官中的神经祖细胞增殖和神经元成熟。组织学测定和单细胞基因表达分析表明，低强度超声可以改善皮质类器官的神经发育。将类器官移植物移植到成年小鼠受损的体感皮层后，纵向电生理记录和组织学分析表明，经过超声处理的类器官移植物会提前成熟。与未治疗组相比，它们还表现出与疼痛相关的伽马带活动增强，并且向宿主大脑的投射更多。最后，低强度超声改善小头畸形脑类器官模型中的神经病理学缺陷。因此，低强度超声刺激促进了大脑类器官的发育和整合，为治疗神经发育障碍和修复皮质损伤提供了策略。