Kook Myung Geun, Lee Seung-Eun, Shin Nari, Kong Dasom, Kim Da-Hyun, Kim Min-Soo, Kang Hyun Kyoung, Choi Soon Won, Kang Kyung-Sun
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
Int J Stem Cells. 2022 Feb 28;15(1):85-94. doi: 10.15283/ijsc21157.
Brain organoids have the potential to improve our understanding of brain development and neurological disease. Despite the importance of brain organoids, the effect of vascularization on brain organoids is largely unknown. The objective of this study is to develop vascularized organoids by assembling vascular spheroids with cerebral organoids.
In this study, vascularized spheroids were generated from non-adherent microwell culture system of human umbilical vein endothelial cells, human dermal fibroblasts and human umbilical cord blood derived mesenchymal stem cells. These vascular spheroids were used for fusion with iPSCs induced cerebral organoids. Immunostaining studies of vascularized organoids demonstrated well organized vascular structures and reduced apoptosis. We showed that the vascularization in cerebral organoids up-regulated the Wnt/-catenin signaling.
We developed vascularized cerebral organoids through assembly of brain organoids with vascular spheroids. This method could not only provide a model to study human cortical development but also represent an opportunity to explore neurological disease.
脑类器官有潜力增进我们对脑发育和神经疾病的理解。尽管脑类器官很重要，但血管化对脑类器官的影响在很大程度上尚不清楚。本研究的目的是通过将血管球与脑类器官组装来构建血管化类器官。
在本研究中，从人脐静脉内皮细胞、人真皮成纤维细胞和人脐带血来源的间充质干细胞的非贴壁微孔培养系统中生成血管球。这些血管球用于与诱导多能干细胞衍生的脑类器官融合。对血管化类器官的免疫染色研究显示血管结构组织良好且细胞凋亡减少。我们发现脑类器官中的血管化上调了Wnt/β-连环蛋白信号通路。
我们通过将脑类器官与血管球组装构建了血管化脑类器官。该方法不仅可为研究人类皮质发育提供模型，也为探索神经疾病提供了契机。
