期刊
TOXICOLOGY IN VITRO
卷 84, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2022.105424
关键词
Blood-brain barrier; Brain microvasculature; iPSC; Transcriptomics; In vitro BBB models
类别
资金
- Marie Sklodowska-Curie Action-Innovative Training Network project in3 [721975]
- Marie Curie Actions (MSCA) [721975] Funding Source: Marie Curie Actions (MSCA)
The blood-brain barrier is a tight barrier at the brain microvascular endothelial cells that restricts access to the brain. Human in vitro BBB models are needed to assess neurotoxicity and drug uptake in the brain. Different protocols for differentiating induced pluripotent stem cells into BBB cells have emerged in the past decade, but further characterization is important.
The blood-brain barrier (BBB) is localized at the brain microvascular endothelial cells. These cells form a tight barrier, limiting the access of cells, pathogens, chemicals, and toxins to the brain due to tight junctions and efflux transporters. As the BBB plays a role in the assessment of neurotoxicity and brain uptake of drugs, human in vitro BBB models are highly needed. They allow to evaluate if compounds could reach the central nervous system across the BBB or can compromise its barrier function. Past decade, multiple induced pluripotent stem cell (iPSC)-derived BBB differentiation protocols emerged. These protocols can be divided in two groups, the one-step protocols, direct differentiation from iPSC to BBB cells, or the two-step protocols, differentiation for iPSC to endothelial (progenitor) cells and further induction of BBB characteristics. While the one-step differentiation protocols display good barrier properties, reports question their endothelial nature and maturation status. Therefore protocol characterization remains important. With transcriptomics becoming cheaper, this may support iPSC-derived model characterization. Because of the constraints in obtaining human brain tissue, good human reference data is scarce and would bear inter-individual variability. Additionally, comparison across studies might be challenging due to variations in sample preparation and analysis. Hopefully, increasing use of transcriptomics will allow in-depth characterization of the current iPSC-BBB models and guide researchers to generate more relevant human BBB models.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据