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REVIEW ARTICLE
Generation of vascularized brain organoids:

Technology, applications, and prospects

Quan-Jing Mei , Jia-Qi Wen , Xiao-Xiao Xu , and Hui-Qi Xie *
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1 Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key
Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
2 Department of Medical Biophysics, The Temerty Faculty of Medicine, University of Toronto, Toronto, M5S 1A8, Ontario, Canada
3 Tianfu Jincheng Laboratory, Chengdu, 610093, China
*Corresponding author: Hui-Qi Xie (xiehuiqi@scu.edu.cn)

Citation: Mei QJ, Wen JQ, Xu XX, Abstract
Xie HQ. Generation of vascularized
brain organoids: Technology, Brain organoids have become important tools for studying neural development
applications, and prospects. Organoid
Res. 2025;1(2):8162. and disease modeling by closely mimicking in vivo brain architecture and function.
doi: 10.36922/or.8162 However, despite their potential, conventional brain organoids lack a vascular
Received: December 24, 2024 system, limiting their physiological relevance and growth due to restricted oxygen
and nutrient supply. Recent advances in generating vascularized brain organoids
Revised: February 13, 2025
(V-Organoids) have sought to overcome such limitations, allowing for more accurate
Accepted: March 14, 2025 modeling of human brain development, neurovascular interactions, and blood–
Published online: April 16, 2025 brain barrier (BBB) function. This article provides a comprehensive review of the
methodologies employed to enhance the vascularization of brain organoids, including
Copyright: © 2025 Author(s).
This is an Open-Access article induction techniques, biomaterials, advanced bioengineering approaches, and in
distributed under the terms of the vivo implantation. The introduction of functional vasculature into brain organoids
Creative Commons Attribution has not only enhanced their survival and maturation but also expanded their utility
License, permitting distribution, and
reproduction in any medium, which in disease modeling, drug screening, and regenerative medicine. We also discuss
provided that the original work is the applications of V-Organoids in the study of neurodevelopmental processes, BBB
properly cited. permeability in neurological disorders, brain cancer, and regeneration applications.
Publisher’s Note: AccScience Despite significant progress made in the development of V-Organoids, challenges
Publishing remains neutral with regard such as vascular maturity, immune integration, longevity, and ethical considerations
to jurisdictional claims in published
maps and institutional affiliations. must be addressed to enable more accurate brain models, which could enhance our
understanding of neurodevelopment and potential treatments.

Keywords: Vascularized brain organoids; Neurovascular interactions; Blood–brain
barrier; Neurological disorders; Regeneration

1. Introduction ethical limitations have restricted the capacity to conduct
invasive research on the human brain, considerably
As the central organ of the nervous system, the human hindering the advancements in understanding its complex
brain represents one of the body’s most complex and function. These restrictions have impeded progress in the
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mysterious organs, distinguished by its remarkable development of treatments for neurological disorders, such
structural and functional intricacy. Its extraordinary as Alzheimer’s disease (AD) and Parkinson’s disease (PD).
diversity of neuronal cell types and synaptic connections
underpins a wide range of functions, from cognition and The advancement of human pluripotent stem cells
emotional regulation to consciousness. This intricate (hPSCs), including human embryonic stem cells (hESCs)
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organization not only distinguishes humans from other and human induced pluripotent stem cells (hiPSCs), which
species but also poses a significant challenge to unraveling exhibit pluripotency and the potential to differentiate into
the underlying mechanisms of brain function. In addition, any cell type, has facilitated the creation of organoids.
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Volume 1 Issue 2 (2025) 1 doi: 10.36922/or.8162