Department of Biomedical and Clinical Sciences, Università di Milano, 20157, Milano, Italy.
Division of Pathology, Ospedale Sacco, Milan, Italy.
Biochem Biophys Res Commun. 2022 Oct 20;626:30-37. doi: 10.1016/j.bbrc.2022.07.112. Epub 2022 Aug 8.
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.
尽管人脑类器官仍然是最接近人类大脑的体外模型，但它也存在一个弱点，即缺乏血管内皮成分，而血管内皮成分在体内会组织形成血脑屏障 (BBB)。由于 BBB 对于控制神经系统的微环境至关重要，因此本研究提出了 BBB 和人脑类器官的共培养。我们利用了一种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，在 Transwell 系统中进行培养。从诱导多能干细胞 (iPSCs) 开始，我们生成了人脑类器官，然后在存在或不存在体外 BBB 模型的情况下对其进行培养，以评估其对人脑类器官成熟的潜在影响。通过形态分析，在 BBB 存在的情况下，人脑类器官的组织比没有 BBB 的对照组更好。这种效果可能是由于脑源性神经营养因子 (BDNF) 引起的，BDNF 是 BBB 血管内皮成分释放的一种神经营养因子，它参与神经发育、神经可塑性和神经存活。
