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dc.contributor.author | Shaji, Maneesha | en |
dc.contributor.author | Tamada, Atsushi | en |
dc.contributor.author | Fujimoto, Kazuya | en |
dc.contributor.author | Muguruma, Keiko | en |
dc.contributor.author | Karsten, Stanislav L. | en |
dc.contributor.author | Yokokawa, Ryuji | en |
dc.contributor.alternative | 玉田, 篤史 | ja |
dc.contributor.alternative | 藤本, 和也 | ja |
dc.contributor.alternative | 六車, 恵子 | ja |
dc.contributor.alternative | 横川, 隆司 | ja |
dc.date.accessioned | 2024-02-14T04:08:56Z | - |
dc.date.available | 2024-02-14T04:08:56Z | - |
dc.date.issued | 2024-02-21 | - |
dc.identifier.uri | http://hdl.handle.net/2433/286979 | - |
dc.description | マイクロ流体デバイスを用いて大脳オルガノイドの血管新生因子を特定 --血管床を活用したMicrophysiological systems (MPS)--. 京都大学プレスリリース. 2024-01-30. | ja |
dc.description.abstract | The lack of functional vascular system in stem cell-derived cerebral organoids (COs) limits their utility in modeling developmental processes and disease pathologies. Unlike other organs, brain vascularization is poorly understood, which makes it particularly difficult to mimic in vitro. Although several attempts have been made to vascularize COs, complete vascularization leading to functional capillary network development has only been achieved via transplantation into a mouse brain. Understanding the cues governing neurovascular communication is therefore imperative for establishing an efficient in vitro system for vascularized cerebral organoids that can emulate human brain development. Here, we used a multidisciplinary approach combining microfluidics, organoids, and transcriptomics to identify molecular changes in angiogenic programs that impede the successful in vitro vascularization of human induced pluripotent stem cell (iPSC)-derived COs. First, we established a microfluidic cerebral organoid (CO)-vascular bed (VB) co-culture system and conducted transcriptome analysis on the outermost cell layer of COs cultured on the preformed VB. Results revealed coordinated regulation of multiple pro-angiogenic factors and their downstream targets. The VEGF-HIF1A-AKT network was identified as a central pathway involved in the angiogenic response of cerebral organoids to the preformed VB. Among the 324 regulated genes associated with angiogenesis, six transcripts represented significantly regulated growth factors with the capacity to influence angiogenic activity during co-culture. Subsequent on-chip experiments demonstrated the angiogenic and vasculogenic potential of cysteine-rich angiogenic inducer 61 (CYR61) and hepatoma-derived growth factor (HDGF) as potential enhancers of organoid vascularization. Our study provides the first global analysis of cerebral organoid response to three-dimensional microvasculature for in vitro vascularization. | en |
dc.language.iso | eng | - |
dc.publisher | Royal Society of Chemistry (RSC) | en |
dc.rights | © The Royal Society of Chemistry 2024 | en |
dc.rights | This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/ | - |
dc.title | Deciphering potential vascularization factors of on-chip co-cultured hiPSC-derived cerebral organoids | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Lab on a Chip | en |
dc.identifier.volume | 24 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 680 | - |
dc.identifier.epage | 696 | - |
dc.relation.doi | 10.1039/D3LC00930K | - |
dc.textversion | publisher | - |
dc.address | Department of Micro Engineering, Graduate School of Engineering, Kyoto University | en |
dc.address | Department of iPS Cell Applied Medicine, Kansai Medical University | en |
dc.address | Department of Micro Engineering, Graduate School of Engineering, Kyoto University | en |
dc.address | Department of iPS Cell Applied Medicine, Kansai Medical University | en |
dc.address | Department of Micro Engineering, Graduate School of Engineering, Kyoto University | en |
dc.address | Department of Micro Engineering, Graduate School of Engineering, Kyoto University | en |
dc.identifier.pmid | 38284292 | - |
dc.relation.url | https://www.t.kyoto-u.ac.jp/ja/research/topics/20240129 | - |
dcterms.accessRights | open access | - |
datacite.awardNumber | 22K18319 | - |
datacite.awardNumber.uri | https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22K18319/ | - |
dc.identifier.eissn | 1473-0197 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.awardTitle | マイクロ流体デバイスを用いた脳卒中チップの作製と患者由来組織を用いた検証 | ja |
出現コレクション: | 学術雑誌掲載論文等 |
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