Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Neurosurgery, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China.
Oxid Med Cell Longev. 2021 Nov 22;2021:6338722. doi: 10.1155/2021/6338722. eCollection 2021.
Traumatic brain injury (TBI) causes a high rate of mortality and disability, and its treatment is still limited. Loss of neurons in damaged area is hardly rescued by relative molecular therapies. Based on its disease characteristics, we transplanted human embryonic stem cell- (hESC-) derived cerebral organoids in the brain lesions of controlled cortical impact- (CCI-) modeled severe combined immunodeficient (SCID) mice. Grafted organoids survived and differentiated in CCI-induced lesion pools in mouse cortical tissue. Implanted cerebral organoids differentiated into various types of neuronal cells, extended long projections, and showed spontaneous action, as indicated by electromyographic activity in the grafts. Induced vascularization and reduced glial scar were also found after organoid implantation, suggesting grafting could improve local situation and promote neural repair. More importantly, the CCI mice's spatial learning and memory improved after organoid grafting. These findings suggest that cerebral organoid implanted in lesion sites differentiates into cortical neurons, forms long projections, and reverses deficits in spatial learning and memory, a potential therapeutic avenue for TBI.
创伤性脑损伤 (TBI) 导致高死亡率和残疾率,其治疗仍然有限。相对分子疗法几乎无法挽救受损区域的神经元。基于其疾病特征,我们将人类胚胎干细胞衍生的脑类器官移植到经控制性皮质撞击 (CCI) 建模的严重联合免疫缺陷 (SCID) 小鼠的脑损伤部位。移植的类器官在 CCI 诱导的损伤池中在小鼠皮质组织中存活并分化。植入的脑类器官分化为各种类型的神经元细胞,延伸出长突起,并表现出自发活动,这可通过移植体中的肌电图活动来指示。类器官植入后还发现了诱导的血管生成和减少的神经胶质瘢痕,这表明移植可以改善局部情况并促进神经修复。更重要的是,类器官移植后 CCI 小鼠的空间学习和记忆能力得到改善。这些发现表明,移植到损伤部位的脑类器官分化为皮质神经元,形成长突起,并逆转空间学习和记忆缺陷,为 TBI 的治疗提供了一种潜在的途径。
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