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2020
Journal Article
Titel
Human iPSC-Derived Blood-Brain Barrier Models: Valuable Tools for Preclinical Drug Discovery and Development?
Abstract
Translating basic biological knowledge into applications remains a key issue for effectively tackling neurodegenerative, neuroinflammatory, or neuroendocrine disorders. Efficient delivery of therapeutics across the neuroprotective blood-brain barrier (BBB) still poses a demanding challenge for drug development targeting central nervous system diseases. Validated in vitro models of the BBB could facilitate effective testing of drug candidates targeting the brain early in the drug discovery process during lead generation. We here review the potential of mono- or (isogenic) co-culture BBB models based on brain capillary endothelial cells (BCECs) derived from human-induced pluripotent stem cells (hiPSCs), and compare them to several available BBB in vitro models from primary human or non-human cells and to rodent in vivo models, as well as to classical and widely used barrier models [Caco-2, parallel artificial membrane permeability assay (PAMPA)]. In particular, we are discussing the features and predictivity of these models and how hiPSC-derived BBB models could impact future discovery and development of novel CNS-targeting therapeutics.
Author(s)
Mathew, Sanjana
University Hospital Würzburg, Chair Tissue Engineering and Regenerative Medicine (TERM), Würzburg, Germany
Hartmann, Carla
University Hospital Halle, University Clinic and Outpatient Clinic for Psychiatry, Psychosomatic Medicine, Halle (Saale), Germany
Jung, Matthias
University Hospital Halle, University Clinic and Outpatient Clinic for Psychiatry, Psychosomatic Medicine, Halle (Saale), Germany
Neuhaus, Winfried
AIT Austrian Institute of Technology GmbH, Center Health and Bioresources, Competence Unit Molecular Diagnostics, Vienna, Austria