TY  - JOUR
A1  - Appelt‐Menzel, Antje
A1  - Oerter, Sabrina
A1  - Mathew, Sanjana
A1  - Haferkamp, Undine
A1  - Hartmann, Carla
A1  - Jung, Matthias
A1  - Neuhaus, Winfried
A1  - Pless, Ole
T1  - Human iPSC‐Derived Blood‐Brain Barrier Models: Valuable Tools for Preclinical Drug Discovery and Development?
JF  - Current Protocols in Stem Cell Biology
N2  - 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.
KW  - blood‐brain barrier (BBB)
KW  - CNS disease
KW  - drug permeability screening
KW  - human‐induced pluripotent stem cells (hiPSC)
KW  - preclinical drug discovery
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218509
VL  - 55
IS  - 1
ER  - 
TY  - JOUR
A1  - Schwedhelm, Ivo
A1  - Zdzieblo, Daniela
A1  - Appelt-Menzel, Antje
A1  - Berger, Constantin
A1  - Schmitz, Tobias
A1  - Schuldt, Bernhard
A1  - Franke, Andre
A1  - Müller, Franz-Josef
A1  - Pless, Ole
A1  - Schwarz, Thomas
A1  - Wiedemann, Philipp
A1  - Walles, Heike
A1  - Hansmann, Jan
T1  - Automated real-time monitoring of human pluripotent stem cell aggregation in stirred tank reactors
JF  - Scientific Reports
N2  - The culture of human induced pluripotent stem cells (hiPSCs) at large scale becomes feasible with the aid of scalable suspension setups in continuously stirred tank reactors (CSTRs). Innovative monitoring options and emerging automated process control strategies allow for the necessary highly defined culture conditions. Next to standard process characteristics such as oxygen consumption, pH, and metabolite turnover, a reproducible and steady formation of hiPSC aggregates is vital for process scalability. In this regard, we developed a hiPSC-specific suspension culture unit consisting of a fully monitored CSTR system integrated into a custom-designed and fully automated incubator. As a step towards cost-effective hiPSC suspension culture and to pave the way for flexibility at a large scale, we constructed and utilized tailored miniature CSTRs that are largely made from three-dimensional (3D) printed polylactic acid (PLA) filament, which is a low-cost material used in fused deposition modelling. Further, the monitoring tool for hiPSC suspension cultures utilizes in situ microscopic imaging to visualize hiPSC aggregation in real-time to a statistically significant degree while omitting the need for time-intensive sampling. Suitability of our culture unit, especially concerning the developed hiPSC-specific CSTR system, was proven by demonstrating pluripotency of CSTR-cultured hiPSCs at RNA (including PluriTest) and protein level.
KW  - Biomedical engineering
KW  - Stem-cell biotechnology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202649
VL  - 9
ER  -