A Biomimetic Human Multi-Cellular In Vitro Model of the Blood–Brain Barrier DOI Open Access

John Saliba,

Jessica Saliba, Marwan El Sabban

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3592 - 3592

Опубликована: Апрель 11, 2025

Current in vitro models fail to recapitulate specific physiological properties of the human blood-brain barrier (BBB); hence need for a reliable platform study central nervous system diseases and drug permeability. To mimic normally tight interface, primary endothelial cells (HAECs) astrocytes (A) were grown confined space physical scaffold created by gelatin methacrylate (GelMA) hydrogel allow optimal astrocyte-endothelial cell direct/indirect interaction. Evidence physiologically relevant BBB was established assessing expression junction markers conferring function, measuring biophysical attributes using trans-endothelial electrical resistance (TEER) Evans blue albumin (EBA) permeability assay. An HAEC+A three-dimensional (3D) co-culture associated with 12-fold higher claudin-5 (CLDN5) cadherin-1 (CDH1 or Epithelial [E]-cadherin) transcriptional levels than two-dimensional (2D) models. This model conferred highest TEER (45 Ω·cm2) 3D HAEC+A, which value 30 Ω·cm2 2D (p < 0.01) 25 HAEC cultures 0.001). Functionally, co-cultures, resulted 10-fold 7-fold lower EBA at 120 min, HAECs alone co-cultures 0.01). The has acquired features mimicking vitro, is now poised be tested pharmacological agents, parasites, (such as brain-tropic cancer metastasis) any mechanisms that might involve traversing BBB.

Язык: Английский

A Biomimetic Human Multi-Cellular In Vitro Model of the Blood–Brain Barrier DOI Open Access

John Saliba,

Jessica Saliba, Marwan El Sabban

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3592 - 3592

Опубликована: Апрель 11, 2025

Current in vitro models fail to recapitulate specific physiological properties of the human blood-brain barrier (BBB); hence need for a reliable platform study central nervous system diseases and drug permeability. To mimic normally tight interface, primary endothelial cells (HAECs) astrocytes (A) were grown confined space physical scaffold created by gelatin methacrylate (GelMA) hydrogel allow optimal astrocyte-endothelial cell direct/indirect interaction. Evidence physiologically relevant BBB was established assessing expression junction markers conferring function, measuring biophysical attributes using trans-endothelial electrical resistance (TEER) Evans blue albumin (EBA) permeability assay. An HAEC+A three-dimensional (3D) co-culture associated with 12-fold higher claudin-5 (CLDN5) cadherin-1 (CDH1 or Epithelial [E]-cadherin) transcriptional levels than two-dimensional (2D) models. This model conferred highest TEER (45 Ω·cm2) 3D HAEC+A, which value 30 Ω·cm2 2D (p < 0.01) 25 HAEC cultures 0.001). Functionally, co-cultures, resulted 10-fold 7-fold lower EBA at 120 min, HAECs alone co-cultures 0.01). The has acquired features mimicking vitro, is now poised be tested pharmacological agents, parasites, (such as brain-tropic cancer metastasis) any mechanisms that might involve traversing BBB.

Язык: Английский

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