In recent years, the field of cell biology developed to such an extent that the need for animal models in preclinical research is reducing. Accelerated development and the use of predictive and robust cellular 2D and 3D models have become standard tools to address important scientific questions without the use of animals. Cells can be grown and modified easily, and they are also commercially available. Advances in culture techniques have made using stably expressing cell lines an easy way to study almost every topic that relates to health and disease. Techniques such as CRISPR allow easy genome editing of cell lines and the introduction of induced pluripotent stem cells (also known as iPS cells or iPSCs) has been a game changer for researching human diseases in a dish.
Heterologous expression of recombinant ion channel subunits in mammalian cell lines such as HEK293, CHO or Jurkat cells, allows for the characterization of their functional properties and pharmacological regulation in various research fields, from neuroscience to cardiac research. Automated patch clamp systems such as the Patchliner and SyncroPatch 384 can be used to screen ion channels expressed in cell lines in a flexible manner and with scalable throughput. This technology facilitates the functional mapping of electrophysiological properties of ion channels and their subunits, as well as screening for the effects of various mutations or compound specificity in the drug discovery process. Recently, researchers at the Victor Chang Cardiac Research Institute used the high-throughput automated patch clamp system, SyncroPatch 384, to develop a new electrical test that can screen hundreds of gene mutations. Using this technique, mutations in ion channel genes that are harmful to the heart in inherited cardiac disorders, which can cause sudden death, can be pinpointed and investigated. The breakthrough is a giant leap forward in the accuracy and precision of genetic testing that has profound implications not only for inherited heart disorders, but a wide range of neurological conditions, and muscle and kidney diseases.
New Screening Test for Those at Risk of Sudden Cardiac Arrest
Prof. Jamie Vandenberg
Organisation: Victor Chang Cardiac Research Institute
Human induced pluripotent stem cells (hiPSCs) are a viable alternative to acutely isolated primary cells because of their recapitulation of native cell behavior, their availability in large numbers and that they are human in origin. What is more, donor cells can be taken directly from patients and differentiated into cell types of interest, for example cardiomyocytes for arrhythmia disorders or neurons for disorders affecting the CNS, and mutations in ion channels can be investigated in a more physiologically relevant environment compared with single ion channel types overexpressed in cell lines. This also paves the way for personalized medicine, whereby drugs can be tested in vitro on patient-derived cells.
Instrument manufacturers and stem cell providers have been working closely together to test and optimize the use of these cell types, to realize their potential in cellular and drug discovery research. The use of stem cell-derived cardiomyocytes and neurons on automated patch clamp devices Port-a-Patch, Patchliner and SyncroPatch 384 from a variety of commercial manufacturers and academic labs has been proven. Stem cell-derived cardiomyocytes and stem cell-derived hepatocytes have been used on the CardioExcyte 96 and FLEXcyte 96 to investigate cardiac safety and toxicity. Stem cell-derived cardiomyocytes and neurons have also been used successfully on the SURFE2R N1 to record organelles such as mitochondria, and transporters.
In some cases acutely isolated primary cells may be required for use in experiments. This includes primary neuronal cultures, astrocytes, synoviocytes, smooth muscle cells and red blood cells. These have all been used successfully on our automated patch clamp instruments. Up until 2022, the use of adult primary cardiomyocytes had not been shown using automated patch clamp but the use of adult primary cardiomyocytes isolated from pig heart on the SyncroPatch 384 was published in Communications Biology by Seibertz et al, paving the way for optimization of this kind of cell type for high throughput screening, and reducing the number of animals required.
Our portfolio of products offers versatile automated tools for in vitro dissection of physiological and pathophysiological cellular phenotypes. The broad range and versatility of cell-based assays easily performed with these automated patch clamp and cell analytics systems, make them an excellent choice for integration into a core cell screening center/therapy/ biomanufacturing facility and traditional academic labs around the globe.
Contact our specialist Dr. Sonja Stölzle-Feix (Product Manager of the CardioExcyte 96, FLEXcyte 96 and Director Scientific Affairs). Sonja is delighted to help you: