A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies
| العنوان: | A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies |
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| المؤلفون: | Aditya Bhalerao, Behnam Noorani, Luca Cucullo, Ehsan Nozohouri, Ulrich Bickel, Snehal Raut |
| المصدر: | Pharmaceutics Volume 13 Issue 9 Pharmaceutics, Vol 13, Iss 1474, p 1474 (2021) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | NVU, Endothelium, endothelium, Pharmaceutical Science, Blood–brain barrier, Rhodamine 123, Article, pericytes, shear stress, drug discovery, chemistry.chemical_compound, Pharmacy and materia medica, stem cells, medicine, Induced pluripotent stem cell, in vitro, co-culture, RS1-441, medicine.anatomical_structure, chemistry, Permeability (electromagnetism), Paracellular transport, Biophysics, Mannitol, Stem cell, medicine.drug, alternative |
| الوصف: | Microfluidics-based organ-on-a-chip technology allows for developing a new class of in-vitro blood-brain barrier (BBB) models that recapitulate many hemodynamic and architectural features of the brain microvasculature not attainable with conventional two-dimensional platforms. Herein, we describe and validate a novel microfluidic BBB model that closely mimics the one in situ. Induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) were juxtaposed with primary human pericytes and astrocytes in a co-culture to enable BBB-specific characteristics, such as low paracellular permeability, efflux activity, and osmotic responses. The permeability coefficients of [13C12] sucrose and [13C6] mannitol were assessed using a highly sensitive LC-MS/MS procedure. The resulting BBB displayed continuous tight-junction patterns, low permeability to mannitol and sucrose, and quasi-physiological responses to hyperosmolar opening and p-glycoprotein inhibitor treatment, as demonstrated by decreased BBB integrity and increased permeability of rhodamine 123, respectively. Astrocytes and pericytes on the abluminal side of the vascular channel provided the environmental cues necessary to form a tight barrier and extend the model’s long-term viability for time-course studies. In conclusion, our novel multi-culture microfluidic platform showcased the ability to replicate a quasi-physiological brain microvascular, thus enabling the development of a highly predictive and translationally relevant BBB model. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1999-4923 |
| DOI: | 10.3390/pharmaceutics13091474 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b6cc55d1f4cb9f243e9691415105a84 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8b6cc55d1f4cb9f243e9691415105a84 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19994923 |
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| DOI: | 10.3390/pharmaceutics13091474 |