The presence of BBB hastens neuronal differentiation of cerebral organoids- The potential role of endothelial derived BDNF
The presence of BBB hastens neuronal differentiation of cerebral organoids- The potential role of endothelial derived BDNF
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DOI：
10.1016/j.bbrc.2022.07.112
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发表时间：
2022-08-12
影响因子：
3.1
通讯作者：
Maier, Jeanette A. M.
中科院分区：
文献类型：
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作者：
Fedele, Giorgia;Cazzaniga, Alessandra;Maier, Jeanette A. M.
尽管仍然是类似于人脑的最佳体外模型，但人脑类器官的弱点是缺乏体内血脑屏障（BBB）中组织的内皮成分。由于血脑屏障对于控制神经系统的微环境至关重要，因此本研究提出了血脑屏障和脑类器官的共培养。我们利用 Transwell 系统中由原代人脑微血管内皮细胞和星形胶质细胞组成的 BBB 模型。从诱导多能干细胞 (iPSC) 开始，我们生成了人脑类器官，然后在不存在或存在 BBB 体外模型的情况下进行培养，以评估对脑类器官成熟的潜在影响。通过形态学分析发现，在 BBB 存在的情况下，大脑类器官的组织性比在 BBB 缺失的情况下的对照更好。这种效应可能是由于脑源性神经营养因子 (BDNF) 所致，这是一种由 BBB 内皮成分释放的神经营养因子，参与神经发育、神经可塑性和神经存活。(c) 2022 Elsevier Inc. 保留所有权利。
Despite remaining the best in vitro model to resemble the human brain, a weakness of human cerebral organoids is the lack of the endothelial component that in vivo organizes in the blood brain barrier (BBB). Since the BBB is crucial to control the microenvironment of the nervous system, this study proposes a co -culture of BBB and cerebral organoids. We utilized a BBB model consisting of primary human brain microvascular endothelial cells and astrocytes in a transwell system. Starting from induced Pluripotent Stem Cells (iPSCs) we generated human cerebral organoids which were then cultured in the absence or presence of an in vitro model of BBB to evaluate potential effects on the maturation of cerebral organoids. By morphological analysis, it emerges that in the presence of the BBB the cerebral organoids are better organized than controls in the absence of the BBB. This effect might be due to Brain Derived Neurotrophic Factor (BDNF), a neurotrophic factor released by the endothelial component of the BBB, which is involved in neurodevelopment, neuroplasticity and neurosurvival.(c) 2022 Elsevier Inc. All rights reserved.