1.Generation of Cortical Brain Organoid with Vascularization by Assembling with Vascular Spheroid
Myung Geun KOOK ; Seung-Eun LEE ; Nari SHIN ; Dasom KONG ; Da-Hyun KIM ; Min-Soo KIM ; Hyun Kyoung KANG ; Soon Won CHOI ; Kyung-Sun KANG
International Journal of Stem Cells 2022;15(1):85-94
Background and Objectives:
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.
Methods:
and Results: 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/β-catenin signaling.
Conclusions
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.