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Tumor Treating Fields (TTFields) induce cell junction alterations in a human 3D in vitro model of the blood-brain barrier
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- In a recent study, we showed in an in vitro murine cerebellar microvascular endothelial cell (cerebEND) model as well as in vivo in rats that Tumor-Treating Fields (TTFields) reversibly open the blood–brain barrier (BBB). This process is facilitated by delocalizing tight junction proteins such as claudin-5 from the membrane to the cytoplasm. In investigating the possibility that the same effects could be observed in human-derived cells, a 3D co-culture model of the BBB was established consisting of primary microvascular brain endothelial cellsIn a recent study, we showed in an in vitro murine cerebellar microvascular endothelial cell (cerebEND) model as well as in vivo in rats that Tumor-Treating Fields (TTFields) reversibly open the blood–brain barrier (BBB). This process is facilitated by delocalizing tight junction proteins such as claudin-5 from the membrane to the cytoplasm. In investigating the possibility that the same effects could be observed in human-derived cells, a 3D co-culture model of the BBB was established consisting of primary microvascular brain endothelial cells (HBMVEC) and immortalized pericytes, both of human origin. The TTFields at a frequency of 100 kHz administered for 72 h increased the permeability of our human-derived BBB model. The integrity of the BBB had already recovered 48 h post-TTFields, which is earlier than that observed in cerebEND. The data presented herein validate the previously observed effects of TTFields in murine models. Moreover, due to the fact that human cell-based in vitro models more closely resemble patient-derived entities, our findings are highly relevant for pre-clinical studies.…
Autor(en): | Ellaine Salvador, Theresa Köppl, Julia Hörmann, Sebastian Schönhärl, Polina Bugaeva, Almuth F. Kessler, Malgorzata Burek, Ralf-Ingo Ernestus, Mario Löhr, Carsten Hagemann |
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URN: | urn:nbn:de:bvb:20-opus-304830 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Neurochirurgische Klinik und Poliklinik |
Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004) | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Pharmaceutics |
ISSN: | 1999-4923 |
Erscheinungsjahr: | 2023 |
Band / Jahrgang: | 15 |
Heft / Ausgabe: | 1 |
Aufsatznummer: | 185 |
Originalveröffentlichung / Quelle: | Pharmaceutics (2022) 15:1, 185. doi:10.3390/pharmaceutics15010185 |
DOI: | https://doi.org/10.3390/pharmaceutics15010185 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | 3D in vitro model; CNS disorders; Tumor-Treating Fields (TTFields); blood-brain barrier; human brain microvascular endothelial cells (HBMVEC); human cells |
Datum der Freischaltung: | 24.04.2023 |
Datum der Erstveröffentlichung: | 04.01.2023 |
Open-Access-Publikationsfonds / Förderzeitraum 2022 | |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |