2020
DOI: 10.1002/cpsc.122
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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 bloodbrain 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 ge… Show more

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Cited by 31 publications
(27 citation statements)
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References 172 publications
(237 reference statements)
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“…8,9 Neuroscience research and clinical translation not only benefit from the feasibility to derive all major neuronal cell types but also from the progress to create more advanced cell cultures such as brain organoids or blood-brain barrier models. [10][11][12] Hence, iPSC technologies have profoundly changed the operation routines of basic, preclinical, and clinical research in neuroscience since their initial discovery in 2006. 13 The cell culturing of these complex systems including the administration of therapeutic agents is commonly performed in regular Petri dishes or multi-well plates.…”
Section: Introductionmentioning
confidence: 99%
“…8,9 Neuroscience research and clinical translation not only benefit from the feasibility to derive all major neuronal cell types but also from the progress to create more advanced cell cultures such as brain organoids or blood-brain barrier models. [10][11][12] Hence, iPSC technologies have profoundly changed the operation routines of basic, preclinical, and clinical research in neuroscience since their initial discovery in 2006. 13 The cell culturing of these complex systems including the administration of therapeutic agents is commonly performed in regular Petri dishes or multi-well plates.…”
Section: Introductionmentioning
confidence: 99%
“…Signalling pathways and associated kinetics of transport are best suited to study by way of monolayers, as these are specific and simple [62]. For establishing structure activity relationships, and, more crucially, for evaluating toxicological profiles, more sensitive models such as iPSC models are warranted due to enhanced sensitivity and the critical nature of the information garnered in guiding subsequent optimisation of leads and generation of safety data as supporting information for clinical testing application submissions [63]. Organoids in particular would seem the optimal candidate for analysing nanotheranostics in tandem with organ-in-chip microfluidics, as they best recapitulate physiological conditions and integrity of the BBB and can be used to precisely determine cellular uptake and biodistribution in related high-throughput assays in a cost-effective manner.…”
Section: Overview Of Current Modelling Approachesmentioning
confidence: 99%
“…In 2012, the first BBB models derived from human-induced pluripotent stem cells (hiPSCs) were invented and are now reaching a level of validation that might make them suitable for utilization in preclinical drug development programs in the pharmaceutical industry. In addition, these models could provide insights into mechanisms of CNS diseases, which are often associated with general or specific pathophysiological alterations at the BBB [see for review ( 83 )].…”
Section: Introductionmentioning
confidence: 99%