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Recent developments of disease and human in vitro models of the blood-brain barrier

: Appelt-Menzel, Antje; Piontek, Jörg; Kraemer, Tobias; Riethmüller, Christoph; Gaiser, Fabian; Neuhoff, Anja; Mahringer, Anne; Thal, Serge; Förster, Carola; Walles, Heike; Metzger, Marco; Neuhaus, Winfried

ALTEX Proceedings 5 (2016), Nr.1, S.7
ISSN: 2194-0479
European Society for Alternatives to Animal Testing (EUSAAT Congress) <17, 2016, Linz>
Fraunhofer IGB ()

Many different in-vitro models of the BBB have been published based on primary cells, immortalized cell lines or tumor cells derived from several species such as bovine, porcine, mouse, rat or even human. However, no standard in-vitro model of the blood-brain barrier (BBB) is established nor broadly accepted, although huge demands from basic research as well as pharmaceutical industry exist. Moreover, there is a great need for validated disease in-vitro models of the blood-brain barrier considering that almost in every neurodegenerative illness the BBB is altered which presumably contributes to the disease’s etiology and progression. The lack of human BBB models mimicking the in-vivo situation close enough is dramatic, especially considering species differences and the need for save data transferability from e.g. rodent preclinical models to the human situation. After the introduction about the BBB and its role in different diseases two novel BBB in-vitro models will be explained in more detail. First, a mouse BBB in-vitro model for ischemia will be introduced comprising characteristics of barrier breakdown, ABC-transporter functionality, morphology and cerebral ischemia relevant enzyme activities by qPCR, western blotting, immunofluorescence microscopy and functional assays [1]. This model was used to investigate therapeutic strategies. Cross-correlation with a mouse model of traumatic brain injury confirmed the usability and most importantly the predictability of the in-vitro model. Second, recent developments of stem cell models highlight the potential to generate human in-vitro BBB models with in-vivo like phenotype paired with high paracellular tightness. As example for this trend a novel human blood-brain barrier in-vitro model will be introduced this is based on cells derived from human induced pluripotent stem cells. In summary, current works show that the development of predictive disease and human in-vitro models of the BBB is feasible and further comprehensive studies may pave the way for these models to reduce the number of animal studies.