Unraveling the influence of astrocytes on endothelial cell transcription: Towards understanding blood-brain barrier in vitro models’ dynamics
In recent years, considerable advancements have been made in developing in vitro models to better understand the complex dynamics of the blood-brain barrier (BBB) and its critical role in neurological health and disease. Incorporating astrocytes into these models introduces an essential layer of com...
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Elsevier
2025-05-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025001406 |
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| author | Laura Nicoleti Zamproni Begüm Gökçe Justina Venckute Larsson Angela Ceballos-Torres Magnus Gram Marimélia Aparecida Porcionatto Anna Herland |
| author_facet | Laura Nicoleti Zamproni Begüm Gökçe Justina Venckute Larsson Angela Ceballos-Torres Magnus Gram Marimélia Aparecida Porcionatto Anna Herland |
| author_sort | Laura Nicoleti Zamproni |
| collection | DOAJ |
| description | In recent years, considerable advancements have been made in developing in vitro models to better understand the complex dynamics of the blood-brain barrier (BBB) and its critical role in neurological health and disease. Incorporating astrocytes into these models introduces an essential layer of complexity, allowing for a more comprehensive investigation of the cellular interactions and regulatory mechanisms that maintain BBB integrity and functionality. Despite these advances, the specific influence of astrocytes on endothelial cells in in vitro systems remains inadequately explored. This study addresses this gap by examining the transcriptional changes in primary human brain microvascular endothelial cells (HBMECs) cocultured with human astrocytes (HAs). Our findings demonstrate that astrocytes profoundly modulate endothelial pathways involved in cell cycle regulation and division while upregulating genes associated with BBB integrity, protective mechanisms, and transporter activity. Furthermore, astrocytes significantly enhanced transendothelial electrical resistance (TEER) and reduced permeability to tracer Cascade Blue dye, confirming their functional impact on BBB models.By providing a comprehensive human primary cell dataset, this research underscores the pivotal role astrocytes play in shaping endothelial cell gene expression and function in contact coculture systems. These results emphasize the necessity of incorporating astrocytes into in vitro BBB models to accurately replicate neurovascular interactions. Ultimately, this study advances our understanding of BBB physiology and highlights the importance of refining in vitro models to better reflect the complexity of the human neurovascular environment, with potential implications for studying neurological disorders and drug delivery strategies. |
| format | Article |
| id | doaj-art-e1814f9a94d44563bc307ba01034befd |
| institution | DOAJ |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-e1814f9a94d44563bc307ba01034befd2025-08-20T03:17:35ZengElsevierBrain Research Bulletin1873-27472025-05-0122411132810.1016/j.brainresbull.2025.111328Unraveling the influence of astrocytes on endothelial cell transcription: Towards understanding blood-brain barrier in vitro models’ dynamicsLaura Nicoleti Zamproni0Begüm Gökçe1Justina Venckute Larsson2Angela Ceballos-Torres3Magnus Gram4Marimélia Aparecida Porcionatto5Anna Herland6Department of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; AIMES – Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, StockholmAIMES – Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden; Department of Bioengineering, Graduate School of Natural and Applied Sciences, Ege University, Izmir, TurkeyDivision of Nanobiotechnology, Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Sweden; AIMES – Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, StockholmDivision of Nanobiotechnology, Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Sweden; AIMES – Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, StockholmDepartment of Clinical Sciences Lund, Pediatrics, Lund University, Lund, Sweden; Department of Neonatology, Skåne University Hospital, Lund, Sweden; Department of Biomedical Science, Faculty of Health and Society, Biofilms – Research Centre for Biointerfaces, Malmö University, Malmö, SwedenDepartment of Biochemistry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDivision of Nanobiotechnology, Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Sweden; AIMES – Center for the Advancement of Integrated Medical and Engineering Sciences at Karolinska Institutet and KTH Royal Institute of Technology, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm; Corresponding author at: Division of Nanobiotechnology, Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Sweden.In recent years, considerable advancements have been made in developing in vitro models to better understand the complex dynamics of the blood-brain barrier (BBB) and its critical role in neurological health and disease. Incorporating astrocytes into these models introduces an essential layer of complexity, allowing for a more comprehensive investigation of the cellular interactions and regulatory mechanisms that maintain BBB integrity and functionality. Despite these advances, the specific influence of astrocytes on endothelial cells in in vitro systems remains inadequately explored. This study addresses this gap by examining the transcriptional changes in primary human brain microvascular endothelial cells (HBMECs) cocultured with human astrocytes (HAs). Our findings demonstrate that astrocytes profoundly modulate endothelial pathways involved in cell cycle regulation and division while upregulating genes associated with BBB integrity, protective mechanisms, and transporter activity. Furthermore, astrocytes significantly enhanced transendothelial electrical resistance (TEER) and reduced permeability to tracer Cascade Blue dye, confirming their functional impact on BBB models.By providing a comprehensive human primary cell dataset, this research underscores the pivotal role astrocytes play in shaping endothelial cell gene expression and function in contact coculture systems. These results emphasize the necessity of incorporating astrocytes into in vitro BBB models to accurately replicate neurovascular interactions. Ultimately, this study advances our understanding of BBB physiology and highlights the importance of refining in vitro models to better reflect the complexity of the human neurovascular environment, with potential implications for studying neurological disorders and drug delivery strategies.http://www.sciencedirect.com/science/article/pii/S0361923025001406Blood-brain barrierHuman astrocytesHuman brain microvascular endothelial cellsTranscriptional changes |
| spellingShingle | Laura Nicoleti Zamproni Begüm Gökçe Justina Venckute Larsson Angela Ceballos-Torres Magnus Gram Marimélia Aparecida Porcionatto Anna Herland Unraveling the influence of astrocytes on endothelial cell transcription: Towards understanding blood-brain barrier in vitro models’ dynamics Brain Research Bulletin Blood-brain barrier Human astrocytes Human brain microvascular endothelial cells Transcriptional changes |
| title | Unraveling the influence of astrocytes on endothelial cell transcription: Towards understanding blood-brain barrier in vitro models’ dynamics |
| title_full | Unraveling the influence of astrocytes on endothelial cell transcription: Towards understanding blood-brain barrier in vitro models’ dynamics |
| title_fullStr | Unraveling the influence of astrocytes on endothelial cell transcription: Towards understanding blood-brain barrier in vitro models’ dynamics |
| title_full_unstemmed | Unraveling the influence of astrocytes on endothelial cell transcription: Towards understanding blood-brain barrier in vitro models’ dynamics |
| title_short | Unraveling the influence of astrocytes on endothelial cell transcription: Towards understanding blood-brain barrier in vitro models’ dynamics |
| title_sort | unraveling the influence of astrocytes on endothelial cell transcription towards understanding blood brain barrier in vitro models dynamics |
| topic | Blood-brain barrier Human astrocytes Human brain microvascular endothelial cells Transcriptional changes |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025001406 |
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