Future strategies include pluripotent stem cell-derived cardiomyocytes
18 Feb 2013

Dietmar Hess holds a degree in biology and has considerable experience in the field of neurophysiology and pharmacology, both in academia and industry. He currently heads the Safety Pharmacology Unit at the NMI TT GmbH (Germany) which focuses on cardiac in vitro and ex vivo models and assays.

The NMI TT GmbH is a GLP/GMP certified contract R&D company, providing dedicated and expert services to customers in the pharmaceutical, biotechnical and medical technology industry.
The facilities at the NMI TT Pharmaservices division encompass electrophysiological assays for preclinical drug development and safety pharmacology, including automated approaches and/or proprietary microelectrode array (MEA)-based technology. Our range extends from single-cell models to the ex vivo level.

NMI TT GmbH building in Reutlingen, Germany


Cardiac ex vivo analysis with NOTOCORD-hem™

NOTOCORD-hem™ software has been continuously used since 2006 to run cardiac ex vivo models, such as Langendorff perfused isolated heart and papillary muscle preparations as well as isolated organ preparations to address functional compound-receptor binding studies. It provides excellent software for signal detection and analysis.
By means of the online analysis feature, it is possible to carry out online quality assessment of a running experiment. The software also facilitates the immediate correction or modification of experiment settings if required. Data extraction from raw data, via the Excel interface, is particularly easy to handle and saves time.

Strategies for the future

The need for new strategies in compound testing is being intensively debated by the pharmaceutical industry.

Cardiomyocytes, generated from induced pluripotent stem cells (iPS cells), open new possibilities for using human material directly in in vitro tests of adverse cardiovascular effects. Since the predictive value of preclinical data is higher, it is expected that this approach will make the translation from in vivo-generated animal data to humans obsolete.
This will lead to fewer animal experiments being done. Moreover, the unlimited availability of human material sources would allow higher throughput approaches.

The electrical activity of stem cell-derived cardiomyocytes (and other electrogenic cell types) can easily be recorded by microelectrode array (MEA) technology. This non-invasive methodology allows the extracellular recording of action potentials from the cells seeded directly on top of the MEA recording electrodes. Parallel recordings from iPS-generated cells on MEAs, in high throughput, produce extensive data that requires automated signal detection and analysis routines.

A: Adult isolated ventricular cardiomyocyte from guinea pig. B: Cardiac action potential from isolated guinea pig cardiomyocytes intracellularly recorded with the patch clamp technique. C: Commercially available human induced pluripotent stem cell derived cardiomyocytes (hiPS) cultivated on the MEA platform. D: Field action potential recorded from the hiPS cardiomyocytes by MEA electrodes.

 

For the pharmaceutical industry, an assay package providing thorough pharmacological validation of well-differentiated iPS-generated cells, and involving robust and fast-recording systems as well as standardized analysis procedures, would inevitably speed up preclinical drug development programmes.
The NMI TT GmbH has long-standing experience, not only in applying MEA technology but also in developing new approaches and assays involving a range of cell types, such as those from brain, heart, gut and the pancreas, either as primary or stem cell-derived cells.

High synergies can be achieved by combining our expertise with NOTOCORD®´s outstanding performance and experience: undoubtedly, sophisticated and powerful signal detection and analysis software could be generated for cellular high-throughput electrophysiological test systems.