Next Generation In Vitro Models of the Human Blood - Brain/Cerebrospinal Fluid Barrier

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Background

The blood-brain barrier (BBB), including the blood-cerebrospinal (BCSFB) fluid barrier, consists of a unique collection of cell types and extracellular matrix that serves a protective function by restricting access to the brain and spinal cord. These barriers function to maintain equilibrium in the brain while maintaining cell health through nutrient delivery, immune protection, and waste elimination. However, its presence presents a difficult obstacle to overcome when developing potential treatment strategies that need to directly access the brain. Animal models have proven useful for foundational research, but they do not truly recapitulate the function of the human BBB/BCSFB system. Human cell-based culture models that can accurately reflect the properties of these barriers are needed, both to provide deeper understanding of the underlying biology of barrier function and as a tool for drug screening in the human brain.



The main applications for human brain-barrier modeling are increasing the physiological relevance of existing cell culture models or for interrogating the integrity of the barrier itself.



Protocols for the formation and culture of three-dimensional neural constructs (organoids and spheroids) have been established. However, these tissues are limited in their growth by the lack of nutrient penetration, resulting in hypoxic gradients and cell death within their cores. This limits the physiological relevance of most human brain tissue and disease modeling applications. This problem is being addressed by cutting edge work to create co-culture models that include endothelial cells, glia, and pericytes that provide a comprehensive and fully perfusable microvasculature that recapitulates key in vivo barrier properties.



The second application focuses on standardized, human relevant models as a tool for drug screening. Such systems can contain multiple compartments mimicking human tissues which can serve as a relevant tool for drug discovery and target validation. Next generation engineering techniques that can standardize and scale-up these quickly developing BBB/BCSFB culture models are needed. Current advances in microfluidic systems and bioprinting aim to create platforms for perfusable cell culture models to address these issues.



We invite submissions related to the topic of developing human in vitro models of the BBB or BCSFB. We welcome many types of manuscripts supported by the journal: perspective pieces, brief research reports, original research, methods, as well as review and mini review articles. Included in this scope are:

- Human primary cell culture and pluripotent stem cell culture derived models of key components of the BBB and BCSFB

- Models that incorporate novel bioengineering approaches to increase standardization, throughput, and complexity of human barrier models

- Diverse applications of human barrier models including development, aging, neurodegeneration, cancer, and injury.

Excluded from the scope of this topic are animal models, non-human animal culture models or human clinical trials (though research with a translational application is welcome).

Keywords: cerebral spinal fluid, choroid plexus, endothelial cells, pericytes, astrocytes, barrier, microfluidics, bioprinting, organoids, angiogenesis, stem cells, neurovascular unit

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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