Applications

Advanced Cardiomyocyte Cell Culture

Discovery, Regenerative Medicine, Toxicity

Advanced cell culture techniques including 3D spheroids, micropatterned co-culture, bioengineered and flow-based systems, and bioprinting offer the potential to better mimic in vivo tissue structure and function. CDI’s cardiomyocytes are amenable to these culture techniques as pure cell populations or in co-culture with other cell types, such as CDI’s iCell Endothelial Cells.

Genetic Manipulation of Cardiomyocytes

Discovery, Regenerative Medicine, Toxicity

The ability to interrogate and monitor gene expression is critical to understanding biological pathways that underlie normal and pathogenic cellular function. CDI’s cardiomyocytes are amenable to various genetic manipulation techniques including transfection, transduction, siRNA, and reporter vector expression.

Monitoring Cardiotoxicity

Discovery, Toxicity

Measurements of cell health are a fundamental component of any disease research and drug development effort. Cell health endpoints represent various biological processes including cell morphology, viability, cytotoxicity, apoptosis, and mitochondrial integrity. In drug development, researchers interrogate these endpoints as part of discovery screening efforts as well as toxicity studies. CDI’s cardiomyocytes have been utilized to measure various cardiac cell health endpoints using platforms including:

• Plate-based fluorescent and luminescent assays
• Metabolism analysis (Seahorse Biosciences XF96)
• High content analysis (Molecular Devices ImageXpress)
• Impedance measurement (ACEA xCELLigence)

Measuring Cardiomyocyte Electrophysiology

Discovery, Toxicity

The dysregulation of ion channel function and electrical signaling is a key cause of congenital, environmental, and drug-induced cardiac dysfunction. CDI’s cardiomyocytes recapitulate in vivo cardiac function and have demonstrated utility in monitoring electrical activity at molecular, cellular, and organotypic levels using platforms including:

• Manual patch clamp
• Automated patch clamp
• Multielectrode array (MEA) (Axion Maestro, Multi Channel Systems MEA60-Inv-BC-System-E)
• Voltage sensitive dyes

Measuring Cardiomyocyte Contractility

Discovery, Toxicity

The modulation of cardiomyocyte contraction (inotropy) is an important phenotypic endpoint for drug discovery, both in the context of intended outcomes and adverse side effects. CDI’s cardiomyocytes have been used to perform direct measurement of cellular movement or indirect measurement of changes in cell morphology using platforms including:

• Calcium handling (Molecular Devices FLIPR, Vala Sciences Kinetic Image Cytometer)
• Calcium and contractility measurement (IonOptix MMSYS)
• Impedance measurement (ACEA xCELLigence)
• Vector motion analysis (Sony Corporation)

Detecting Cardiomyocyte Arrhythmia

Discovery, Toxicity

The development of cardiac arrhythmias as an unintended pharmacological side effect is the most common cause of drug withdrawal and restrictions placed on marketed drugs. CDI’s cardiomyocytes have emerged as the most physiologically relevant and predictive human in vitro model system for detecting drug-mediated arrhythmias. Researchers have demonstrated the utility of these cardiomyocytes for this application using platforms including:

• Manual patch clamp
• Multielectrode array (MEA) (Axion Maestro, Multi Channel Systems MEA60-Inv-BC-System-E)
• High content analysis (Molecular Devices ImageXpress)
• Impedance measurement (ACEA xCELLigence)
• Image cytometry (Vala Sciences Kinetic Image Cytometer)
• Calcium transient monitoring (Molecular Devices FLIPR)
• Motion vector analysis (Sony Corporation)

Measuring Intracellular Signaling in Cardiomyocytes

Discovery, Toxicity

Various intracellular Ca²⁺ and phosphorylation-mediated signaling pathways play a central role in translating electrical signals at the cell membrane into physical contractile function. These pathways can be measured in CDI’s cardiomyocytes using platforms including:

• Calcium handling (Molecular Devices FLIPR, Vala Sciences Kinetic Image Cytometry)
• High-throughput, functional drug screening (Hamamatsu FDSS)
• Multimode plate reader and detection assays (Perkin Elmer Enspire, AlphaLISA/AlphaScreen)

Advanced Neural Cell Culture

Discovery, Regenerative Medicine, Toxicity

Advanced cell culture techniques including 3D spheroids, micropatterned co-culture, bioengineered and flow-based systems, and bioprinting offer the potential to better mimic in vivo tissue structure and function. CDI’s neurons are amenable to these culture techniques as pure cell populations or in co-culture with other cell types, such as CDI’s astrocytes.

Genetic Manipulation of Neurons

Discovery, Regenerative Medicine, Toxicity

The ability to interrogate and monitor gene expression is critical to understanding biological pathways that underlie normal and pathogenic cellular function. CDI’s neurons and dopaneurons are amenable to various genetic manipulation techniques including:

• Transfection
• Transduction
• siRNA
• Reporter vector expression

Measuring Hematopoietic Cell Proliferation (CFU/CFC Assays)

Discovery, Toxicity

The ability to model human hematopoietic cell differentiation is critical for many areas of biomedical research including drug-induced hematopoietic cell toxicity, bone marrow transplant tolerance, cancer immunotherapy, and autoimmune disorders. CDI’s hematopoietic progenitor cells offer access to commercial quantities of highly pure hematopoietic cells, providing reproducible results for these and other research and therapeutic applications.

Measuring Cardiac Progenitor Cell Proliferation and Differentiation

Discovery, Regenerative Medicine, Toxicity

The ability to model human cell and organ developmental pathways is critical to understanding developmental toxicities and disease pathways and to developing therapeutic strategies for tissue regeneration. CDI’s cardiac progenitor cells are multipotent cardiomyocyte precursor cells that exhibit robust and measurable proliferation and differentiation. Assays with these cells are being used in targeted and phenotypic screens to identify therapeutic candidates for cardiac regeneration.

Measuring Drug Metabolism

Toxicity

Drug metabolism is a key function of the human liver and is largely accomplished via the activity of P450 cytochromes and other enzymes within hepatocytes. Understanding drug metabolism pathways is critical to defining the availability of therapeutic agents and identifying toxic metabolites. CDI’s hepatocytes exhibit P450 activity that is sustained for over 7 days in culture. In addition, functional P450 induction in response to known inducers has been demonstrated.

Monitoring Neurotoxicity

Discovery, Toxicity

Measurements of cell health are a fundamental component of any disease research and drug development effort. Cell health endpoints represent various biological processes including cell morphology, viability, cytotoxicity, apoptosis, and mitochondrial integrity. In drug development, researchers interrogate these endpoints as part of discovery screening efforts and toxicity studies. CDI’s neurons, dopaneurons, and astrocytes have been utilized to measure various neural cell health endpoints using platforms including:

• Plate-based fluorescent and luminescent assays
• Metabolic analysis (Seahorse Biosciences XF96)
• High content analysis (Molecular Devices ImageXpress)

Monitoring Hepatotoxicity

Toxicity

Unforeseen liver toxicity is a primary mode of clinical failure for drugs in development. The long-term stability of CDI’s hepatocytes in culture affords the opportunity to perform repeat dosing at physiologically relevant concentrations to aid in the identification of drug toxicity. Specific mechanisms of hepatotoxicity, such as cell viability, mitochondrial toxicity, and phospholipidosis, can be measured using platforms including:

• Plate-based fluorescent and luminescent assays
• Metabolic analysis (Seahorse Biosciences XF96)
• High content analysis (Molecular Devices ImageXpress)

Genetic Manipulation of Hepatocytes

Discovery, Regenerative Medicine, Toxicity

The ability to interrogate and monitor gene expression is critical to understanding biological pathways that underlie normal and pathogenic cellular function. CDI has evaluated various genetic manipulation tools to enable the development of assays using its hepatocytes.