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These organoids contain different cell types, including neurons and glia, similar to those found in the human brain. Human brain organoids provide unique opportunities to model features of human brain development that are not well-reflected in animal models. Compared with traditional cell cultures and animal models, brain organoids offer a more accurate representation of human brain development and function, rendering them suitable models for neurodevelopmental diseases. In particular, brain organoids derived from patients\u2019 cells have enabled researchers to study diseases at different stages and gain a better understanding of disease mechanisms. Multi-brain regional assembloids allow for the investigation of interactions between distinct brain regions while achieving a higher level of consistency in molecular and functional characterization. Although organoids possess promising features, their usefulness is limited by several unresolved constraints, including cellular stress, hypoxia, necrosis, a lack of high-fidelity cell types, limited maturation, and circuit formation. In this review, we discuss studies to overcome the natural limitations of brain organoids, emphasizing the importance of combinations of all neural cell types, such as glia (astrocyte, oligodendrocytes, and microglia) and vascular cells. Additionally, considering the similarity of organoids to the developing brain, regionally patterned brain organoid-derived neural stem cells (NSCs) could serve as a scalable source for cell replacement therapy. We highlight the potential application of brain organoid-derived cells in disease cell therapy within this field.<\/jats:p>","DOI":"10.3390\/ijms241512528","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T12:26:39Z","timestamp":1691497599000},"page":"12528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Application of Human Brain Organoids\u2014Opportunities and Challenges in Modeling Human Brain Development and Neurodevelopmental Diseases"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4156-3446","authenticated-orcid":false,"given":"Soo-hyun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Seoul 04763, Republic of Korea"},{"name":"Biomedical Research Institute, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Yoon","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Seoul 04763, Republic of Korea"},{"name":"Biomedical Research Institute, Hanyang University, Seoul 04763, Republic of Korea"},{"name":"Department of Premedicine, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea"},{"name":"Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul 04763, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41380-018-0125-2","article-title":"Molecular windows into the human brain for psychiatric disorders","volume":"24","author":"Egervari","year":"2019","journal-title":"Mol. 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