Our collaboration partner Ncardia is offering iPSC-derived cells for Assays on Nanion's Instruments

logo NCardia

Ncardia believes that stem cell technology will help to get better medicines to patients faster. Ncardia develops produces & commercialises highly predictive human cellular assay systems for safety and efficacy testing. The cardiac product portfolio encompasses a broad panel of hiPSC-derived cardiac and neural cell types. In addition, the company delivers the Cardioplate™ product line of quality controlled ready to use assay plates. Ncardia delivers working assay solutions & extensive support.


The following cells were validated on Nanion's Instruments:

Cardiac cells
In order to translate an in vitro cardiac cellular model into the correct clinical interpretation of assay read-outs, a fully functional and validated model is needed. This is assured by all of our cardiomyocytes which are fully functional human iPSC-derived cardiomyocytes produced under a stringent quality manufacturing system.

CardioPlate™
CardioPlate™ is a product line of pre-seeded hiPSC-derived cardiomyocytes (Pluricyte® or Cor.4U® Cardiomyocytes) on different plate formats. These plates are ready-to-use for a variety of different assays for predictive safety pharmacology, toxicity testing and efficacy screening early in drug discovery and development.

Neural cells
Ncardia’s neural cell portfolio offers 3 relevant cell types that can be used for different structural and functional toxicity assays and CNS disease modeling. All our neural cells have been validated in different morphological and electrophysiological assays. Below you can find an overview of our neural cell types derived from human induced pluripotent stem cells (hiPSC).


Collaborative Activities with Ncardia

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NCX1 - Current traces recorded from Cor.4U Cardiomyocytes, iCell Cardiomyocytes and HEK cells

NCX1 Cor4U icell HEK

Icon N1   SURFE2R N1 data and applications:

Cardiac NCX1 was activated using 30 μM Ca2+ on the SURFE2R N1. NCX1 was recorded from Cor.4U® Cardiomyocytes, iCell® Cardiomyocytes2 or overexpressed in HEK cells. The calcium affinity was determined for NCX1 recorded from iCell® Cardiomyocytes2 and HEK cells, shown on the right.  

 

NCX1 - Block by KB-R7943

NCX1 KBR7943 iCell Cor4U HEK

Icon N1   SURFE2R N1 data and applications:

Cardiac NCX1 expressed in iCell® Cardiomyocytes2, Cor.4U® Cardiomyocytes or HEK cells was blocked by increasing concentrations of KB-R7943.  

 

NCX1 - Block by SEA0400

NCX1 iCell HEK SEA0400

Icon N1   SURFE2R N1 data and applications:

Cardiac NCX1 expressed in iCell® Cardiomyocytesor HEK cells was blocked by increasing concentrations of SEA0400, a specific blocker of NCX.  

 

2018 - Combining electrophysiology and contractility recordings for more complete assessment of hiPSC-CMs

icon sp96   SyncroPatch 384PE,   icon pl   Patchliner and   Icon CardioExcyte 96 simpel RGB   CardioExcyte 96 poster, Europhysiology Meeting 2018  logo pdf   (1.4 MB)

2018 - A Sensor Based Technique for Pharmacological Safety Testing of Cardiac Transport Proteins NCX, NaKATPase and Respiratory Chain Complexes

Icon CE   CardioExcyte 96 and   Icon 96SE   SUFE²R 96SE poster, SPS 2018  logo pdf   (1.7 MB)

19.09.2018 | Nanion Technologies and Ncardia Sign Co-Marketing and Support Agreement to enhance Options for Cardiac Researchers

MUNICH, Germany and COLOGNE, Germany, September 19, 2018-- Nanion Technologies GmbH, a leading provider of instrumentation for ion channel drug discovery and screening, and the Ncardia Group, a leading developer, manufacturer, and service provider of human induced pluripotent stem cells (iPSCs) for safety and efficacy testing announced today that they have entered into a joint marketing and sales promotion agreement.

Anika Duenbostell-Schmidt - Statement about the CardioExcyte 96

Icon CE   "I use the CardioExcyte 96 weekly to test substances on our human iPSC-derived cardiomyocytes. It allows me to map, compare and evaluate a wide variety of pharmacological responses with a high degree of reliability and uniformity, and evaluate them through the rapid analysis function."

Anika Duenbostell-Schmidt, Head QC at Ncardia 
Ncardia, Cologne, Germany.

2018 - Investigating pain pathways by inhibition of voltage-gated sodium channels

icon sp96   SyncroPatch 384PE and   icon pl   Patchliner poster, FENS Meeting 2018  logo pdf   (2.5 MB)

2017 - Cardiomyocytes in Voltage Clamp and Current Clamp by Automated Patch Clamp

icon sp96   SyncroPatch 384PE and   icon pl   Patchliner poster, BPS Meeting 2017  logo pdf   (1.7 MB)

2018 - Cross-site comparison of excitation-contraction coupling using impedance and field potential recordings in hiPSC cardiomyocytes

Icon CE   CardioExcyte 96 publication in Journal of Pharmacological and Toxicological Methods (2018)

Authors:
Bot C.T., Juhasz K., Haeusermann F., Polonchuk L., Traebert M., Stölzle-Feix S.

2018 - Optogenetic control of transiently transfected hiPSC-derived cardiomyocytes for the assessment of drug related cardiotoxicity

Icon CE   CardioExcyte 96 presentation (slide deck)   logo pdf   (1.4 MB)

2017 - Cross-site comparison of myocyte phase II compounds on different iPS cardiomyocytes based on CardioExcyte 96 recordings

Icon CE   CardioExcyte 96 presentation (slide deck)   logo pdf   (2.2 MB)

2017 - HTS in Cardiac Safety

Icon CE   CardioExcyte 96 presentation (slide deck)   logo pdf   (4.0 MB)

Dr. Ralf Kettenhofen - Statement about the CardioExcyte 96

Icon CE   "CardioExcyte 96 is an easy-to-use system, providing impedance-based and MEA-like cardiac safety data from a diversity of stem cell-derived cardiomyocytes, and constitutes an excellent complement to automated patch clamp-based safety screening. Concentration- and time-dependence of a compound’s potential cardiotoxicity can efficiently be obtained where the alteration of beating patterns can give a hint as to which cardiac ion channel(s) is affected, after which detailed electrophysiology investigations can be undertaken. Cardiac network responses offer a comprehensive view of a compound’s safety profile, without having to use in-vivo methods, which saves time, costs and suffering. Further on, the powerful software, used for recordings and analysis, employs comprehensive beat investigation algorithms, displaying detailed beating kinetics in real-time. Data handling and export is straightforward, easy to grasp and yet very, very powerful."

Dr. Ralf Kettenhofen, Head of Laboratory 
Ncardia, Cologne, Germany.

2017 - An impedance-based approach using human iPSC-derived cardiomyocytes significantly improves in vitro prediction of in vivo cardiotox liabilities

Icon CE  CardioExcyte 96 publication in Toxicology and Applied Pharmacology (2017)

Authors: 
Koci B., Luerman G., Duenbostell A., Kettenhofen R., Bohlen H., Coyle L., Knight B., Ku W., Volberg W., Woska Jr. J.R., Brown M.P.

2016 - Next level toxicity screening: From single channel to overall cell behavior

Icon Orbit Mini   Orbit mini,   Icon CE   CardioExcyte 96 and   icon sp96   SyncroPatch 384PE poster, Meeting of the French Society of Toxinology (SFET) 2015  logo pdf   (0.9 MB)

2016 - Automated Patch Clamp Meets High-Throughput Screening: 384 Cells Recorded in Parallel on a Planar Patch Clamp Module

icon sp96  SyncroPatch 384PE publication in Journal of Lab Automation (2016)

Authors: 
Obergrussberger A., Brüggemann A., Goetze T.A., Rapedius M., Haarmann C., Rinke I., Becker N., Oka T., Ohtsuki A., Stengel T., Vogel M., Steindl J., Mueller M., Stiehler J., George M., Fertig N.

2015 - Novel screening techniques for ion channel targeting drugs

icon pl  Patchliner,   icon sp96   SyncroPatch 384PE and   Icon CE   CardioExcyte 96 publication in Channels (2015)

Authors: 
Obergrussberger A., Stölzle-Feix S., Becker N., Brüggemann A., Fertig N., Möller C.

2013 - Automated Planar Patch Clamp

icon pl   Patchliner book chapter in Ion Channels (2013)

Authors: 
Milligan, C. J., Möller, C.

2013 - Minimized cell usage for stem cell-derived and primary cells on an automated patchclamp system

icon pl  Patchliner publication in Journal of Pharmacological and Toxicological Methods (2013)

Authors: 
Becker N., Stoelzle S., Göpel S., Guinot D., Mumm P., Haarmann C., Malan D., Bohlen H., Kossolov E., Kettenhofen R., George M., Fertig N., Brüggemann A.

2015 - New Easy-to-Use Hybrid System for Extracellular Potential and Impedance Recordings.

Icon CE  CardioExcyte 96 publication in Journal of Laboratory Automation (2015)

Authors: 
Doerr L., Thomas U., Guinot D.R., Bot C.T., Stoelzle-Feix S., Beckler M., George M., Fertig N.

Neurons - "Peri.4U and Dopa.4U stem cell-derived neurons recorded on Nanion´s Patchliner"

icon pl   Patchliner application note:   logo pdf   (0.6 MB)
Cells were kindly provided by Axiogenesis.  

Cardiomyocytes - "Voltage and current clamp recordings of Cor.4U human iPS cell-derived cardiomyocytes on Nanion’s Patchliner"

icon pl   Patchliner application note:   logo pdf   (0.6 MB)
Cells were kindly provided by Axiogenesis.

Cardiomyocytes - "Impedance and EFP recordings of Cor.4U cells using Nanion’s CardioExcyte 96"

Icon CE   CardioExcyte 96 Application Note   logo pdf   (1.3 MB)
Cells were kindly provided by Ncardia.  

Cardiac Ion Channels - Pharmacology of Sodium Channels

p35 1 CorAticon pl   Patchliner data and applications:
Cells (Cor.AT) were kindly provided by Axiogenesis.

The pharmacology of dibucaine was investigated by the application of 0.3, 1, 3, 10 μM in the presence of 10 μM nifedipine (L-type Ca2+-current blocker). Two control additions of nifedipine (10 μM) were made before the addition of increasing concentrations of dibucaine. The IC50 value was determined as 355 ± 40 nM (n=3), which is in accordance with the literature.

Cardiac Ion Channels - Recordings from SC-Derived Cardiomyocytes

p34 4 actPot

icon pl   Patchliner data and applications:
Cells were kindly provided by Ncardia.

The left picture shows a typical action potential from Cor.At® cardiomyocytes. Whole cell currents recorded in the voltage clamp mode reveal cardiomyocyte-typical ion channels (right). The traces represent mERG-, L-type Ca2+- (blue, block by 50 μM nifedipine), Na+- and K+-currents (from top left to bottom right).

 

Cardiac Action Potentials - Cor.At® Cells

p14 2 CorAT

icon pap   Port-a-Patch data and applications:
Cells were kindly provided by Axiogenesis

Cor.At® cardiomyocytes are derived from mouse embryonic stem (ES) cells. Whole cell currents recorded in voltage clamp mode reveal cardiomyocyte-typical ion channels (K+, Ca2+ and Na+). Traces on the lower left show prolongation of the action potential upon application of Dofetilide (1 μM).

Download: Application Note

Cardiac Action Potentials - From SC-Derived Cardiomyocytes

AN Patchliner CorAtCardiomyocytes 1

 icon pl   Patchliner data and applications:
Cells were kindly provided by Ncardia.

Action potentials recorded from stem-cell derived cardiomyocyetes (Cor.At® cardiomyocytes). Action potentials are triggered by small current pulses. Effects of quinidine and lidocaine on the action potentials are shown.

  

Cardiomyocytes - "Recordings of action potentials in mouse ES cell-derived Cor.At cardiomyocytes on Nanion's Patchliner"

icon pl   Patchliner application note:   logo pdf   (0.7 MB)
Cells were kindly provided by Axiogenesis.  

Cardiomyocytes - "Action Potentials in Mouse ES Cell-Derived Cor.At Cardiomyocytes on Nanion´s Port-a-Patch"

icon pap   Port-a-Patch application note:   logo pdf   (0.6 MB)
Cells were kindly provided by Axiogenesis.

Cardiomyocytes - Data from different cell providers

Icon CE   CardioExcyte different ProvidersCardioExcyte data and applications:
Cells were kindly provided by Axiogenesis, Cellular Dynamics, GE Healthcare, Pluriomics, ReproCell, Takara Bio Cellartis Clonetech.

The CardioExcyte 96 allows for
• Non-invasive, label-free measurements of beating cardiomyocyte networks
• 96 recording wells in parallel with 1 ms time resolution
• Quick experiments or long-term compound effects on cardiotoxicity
• Real-time access to beating parameters
• Outstanding software for data analysis and export
• Cost effcient consumables - 96-well format

Cardiomyocytes - Time-dependent effect of Pentamidine on Cor.4U cardiomyocytes

Icon CE   CardioExcyte Cor4U PentamidineCardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

Time-dependent effect of Pentamidine on Cor.4U cardiomyocytes. Pentamidine clinically causes acquired long QT syndrome, which is associated with prolonged QT intervals, tachycardias, and sudden cardiac arrest. Pentamidine delays terminal repolarization in human heart by acutely blocking cardiac inward rectifier currents. At the same time, it reduces surface expression of the cardiac potassium channel IKr/human ether à-go-go-related gene (hERG).
Insets: EFP raw traces and online analysis value FPDc in the presence of Pentamidine (10 µM) at different timepoints.

Cardiomyocytes - Tetracaine dose response curves as recorded with Cor.4U cells

Icon CE   Tetracaine Cor4UCardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

Impedance amplitude is not changed by addition of increasing concentrations of Tetracaine (left panel), while beat rate of Cor.4U® cells is decreasing. For example, 29.6µM of Tetracaine decreased the beat rate by ~60% when compared to pre-addition values. Cumulative dose-response relationships indicate Tetracaine potency for same-well additions. Representative raw traces for impedance signals (middle panel) clearly indicate a decrease in cell monolayer beat rate with increasing concentrations of Tetracaine.
Extracellular Field Potential (EFP) spike amplitude is decreased by cumulative Tetracaine dose applications to the same monolayer of Cor.4U® hIPSC-CMs (top right), in agreement with compound mechanism of action. Representative raw traces for EFP signals (bottom graph) clearly indicate a decrease in spike amplitude.

Cardiomyocytes - Nifedipine and its concentration dependent effect on Cor.4U cells

Icon CE   Nifedipine Cor4UCardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

Nifedpinie is a dihydropyridine calcium channel blocker that primarily blocks L-type calcium channels. Impedance and EFP recordings on Cor.4U cells reveal a concentration dependent effect on impedance amplitude, beat rate and also a shortening of the FPD as expected.

Cardiomyocytes - Optogenetics meets cardiac safety

Icon CE   CardioExcyte Optogenetics 1CardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

The stimulating optical lid, CardioExcyte 96 SOL, uses LEDs for spatially uniform stimulation of cells transfected with light-gated ion channels such as Channelrhodopsin2 (ChR2).

Right graph: LPM – Light pulse per minute plotted against the recorded beat rate (average of 96 wells). ChR2 transfected Cor.4U cells are following the optical pace rate.

Cardiomyocytes - Channelrhodopsin 2 (ChR2) transfected Cor.4U cells and optical pacing

Icon CE   CardioExcyte Optogenetics 2CardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

ChR2 transfected Cor.4U cells are following the optical pace rate.

Raw data traces upon a 1 Hz, 1.5 Hz, 2 Hz., 2.5 Hz and 3 Hz stimulation rate, extracellular field potentials (top) and impedance (bottom).

 

 

 

Cardiomyocytes - Myocyte phase II study: CiPA conform analysis and arrhythmia detection

Icon CE   CardioExcyte CiPAII 1CardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

Nanion developed a CiPA conform analysis for the Myocyte phase II study. The feature comes along is included in our CiPA analysis routine. Automated arrhythmia detection is just one highlight out of many when it comes to the CardioExcyte 96 software.

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