In this article:
- The Cardio.Force Technology
- Cardio.Force’s Efficiency
- The Existing “Gold Standard” for Cardiac Force Assessment
- Cor.4CE Technology Overview
- Additional Advantages of the Cardio.Force Assay Service
Contractile Force of the Heart | Cardio.Force Service
The Cardio.Force Technology
Cardio.Force is based on the Axiogenesis’s 8-channel Cor.4CE assay device. Currently, 96 well versions are in development for an increased cardiac output and the reduction of cost per data point.
The utility of the technology was exemplified in a publication by Goßmann et al., “Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells.” In the study, Goßmann concludes, “The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data.”
Cardio.Force’s Efficiency
Such assay systems comprise the only cost-effective human in vitro technology that can measure the true cardiac contractile force of the heart. To date, common assay systems for quantitative measurement of contractility have been animal-based, which drive up cost and complexity. In contrast, the Cardio.Force assay offers an efficient system for pharmacological and toxicological studies using human cells that would otherwise require animal models or be more expensive/costly and with few cardiac outputs.
Cor.4U® human iPSC-derived cardiomyocytes are plated on extremely thin and highly flexible membranes for assessment of mechanobiological properties.
The Existing “Gold Standard” for Cardiac Force Assessment
Currently, the “Gold Standard” in toxicology and physiology has been isolated animal heart (Langendorff) preparations for contractility measurements. The Langendorff heart assay is a common in vitro approach used in pharmacological and physiological testing that allows cardiac contractile strength and heart rate to be determined without requiring an intact animal.[i] The major disadvantages of this system are that it is still an animal model, is expensive, is costing $5-20K per compound, is technically challenging, and has relatively high variability.
Other emerging technologies using iPSC-derived cardiomyocytes require very high numbers of cells creating microtissues that make the technology very expensive, while the Cor.4CE system requires only 300K cells per sample measurement.
The Cor.4CE system is also reproducible and scalable, which gives it further cost advantages.
Secondary readouts that are being championed/currently pursued for analyzing and assessing cardiac contractility include impedance measurements, atomic force measurements, movement, and calcium flux analysis. These systems fail to consistently correlate with clinical data; in contrast, the Cor.4CE system does show the expected results including a positive frequency force relationship in reaction to beta-adrenergic stimulation (e.g., isoproterenol) can be observed, proving true force measurement.
Cor.4CE Technology Overview
The Axiogenesis’s Cor.4CE device involves the culture of validated human iPSC-derived cardiomyocytes (Cor.4U) on flexible membranes for a more physiological system. The Axiogenesis Cor.4CE Analysis software allows for derivation of the true contractile force of the heart from the measurement of the displacement of the membrane generated by the contracting cardiomyocytes. It allows for repeatable contractility measurements with unprecedented accuracy under physiological mechanical conditions. Optionally, Cor.4U cardiomyocytes can be co-cultured with Cor.4U fibroblasts in order to increase the physiological relevance of the cell system.
Additional Advantages of the Cardio.Force Assay Service
- True force measurement in human iPSC-derived cardiomyocytes using proprietary Cor.4CE assay technology
- Highly precise, standardized, and repeatable test system in defined/controlled culture conditions
- Sensitive and predictive for cardiac safety pharmacology
- Suitable for scale-up given low compound volumes, quick turnaround
In summary, the combination of Cor.4U with the Cor.4CE system is the first in vitro assay setup to measure the true contractile force of the heart of iPSC-derived cardiomyocytes in a system suitable for scale-up. The system provides an ideal tool to assess pharmacological, safety pharmacological, and toxicological effects of drug candidates on human cardiomyocytes.
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Footnote
[i] Bell, R., Mocanu, M. & Yellon, D. Retrograde heart perfusion: The Langendorff technique of isolated heart perfusion. Journal of Molecular and Cellular Cardiology 50, 940-950 (2011).
Editor’s Note: This post was originally published on February 1, 2017, and has been updated for quality and relevancy.