International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Generation of Cortical Brain Organoid with Vascularization by Assembling with Vascular Spheroid

  • Myung Geun Kook (Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University) ;
  • Seung-Eun Lee (Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University) ;
  • Nari Shin (Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University) ;
  • Dasom Kong (Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University) ;
  • Da-Hyun Kim (Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University) ;
  • Min-Soo Kim (Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University) ;
  • Hyun Kyoung Kang (Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University) ;
  • Soon Won Choi (Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University) ;
  • Kyung-Sun Kang (Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University)
  • Received : 2021.09.15
  • Accepted : 2021.12.11
  • Published : 2022.02.28
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Abstract

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.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1A4A4078907). The funders had no role in the study design, analysis, interpretation and submission of data.

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