Hong Kong University of Science and Technology, United States
Abstract: Brain organoids represent a transformative tool for studying human brain development, offering a physiologically relevant in vitro model to explore complex cellular features and functionality. However, existing models are hindered by limitations, including the inability to replicate all features of the human brain, absence of critical cell types like vascular cells, and significant variability in organoid size and cellular composition between batches. Incorporating vasculature within brain organoids is pivotal for advancing these models by mitigating necrotic cores, promoting nutrient and oxygen exchange, and supporting enhanced maturation.
To address these challenges, we developed a protocol integrating microfluidic chip technology with brain organoid culture to construct a vascularized and standardized brain in vitro model. Our approach enables the formation of an on-chip vascular network that effectively penetrates into the organoid, establishing a physiologically relevant interface. Immunocytochemistry (ICC) and sequencing analyses confirm that vascularization not only supports cellular diversity but also significantly enhances the maturation of brain organoids, with gene expression profiles aligned with advanced developmental stages. This method ensures reproducibility across experimental settings and offers a robust platform for scalable drug screening and precision medicine applications. These findings underscore the transformative potential of vascularized brain organoids for advancing neuroscience research and therapeutic discovery.
Funding Source: Hong Kong Research Grants Council; HKUST Center for Aging Science
