More humanized approach rather than relying on animals
Ischemic heart disease often causes heart attacks and most deaths worldwide. The condition manifests when the heart muscle fails to receive adequate oxygen and eventually starts giving way. Scientists test animals such as rats and mice to study ischemic heart disease. However, there are pumping differences between the rodent and human heart, demanding a more “humanized” model.
Now, a research team led by Research Associate Professor TAKAHASHI Ken, Professor NARUSE Keiji, and a team at Okayama University has created such a model using human stem cells. In a video-based study, researchers use stem cells to create a model of ischemic heart disease that closely replicates cardiac cells under stress.
Stem cells have the unique ability to grow into any kind of specialized cell if given the right cocktail of growth factors.
How was the experiment conducted?
The research team applied the above property of stem cells and transformed them into heart muscle cells, or cardiomyocytes. To do so, human induced pluripotent stem cells (hiPSCs), a subset of stem cells, were first grown in incubators. Steadily growing hiPSCs were then differentiated into cardiomyocytes using a mix of factors promoting cardiac cell growth and subsequently incubated for 30 days. After this period, the cells were observed under a microscope to find that almost half of them had started contracting spontaneously, a property native to cardiomyocytes. Additionally, chemical assays showed that the cells were positive for cellular markers typically found within cardiac cells.
To then induce ischemic heart disease, the newly formed cardiomyocytes were grown in a medium deprived of glucose, their primary energy source. Next, nitrogen gas was gradually released into the incubators holding the cells for 24 hours, creating a hypoxic environment. When observed again, only a small number of viable cells remained which were accompanied by a conspicuous reduction in contractility. Ischemia was thus successfully simulated, closely replicating the cell death that develops in ischemic cardiac disease.
This study reports a novel and clinically relevant technique for studying ischemic cardiac disease in the laboratory. The condition was induced in cardiomyocytes derived from human stem cells mimicking patterns of damage seen in the human heart. This platform can eliminate the need for conducting complex procedures in animals and circumvent animal sacrifice. Moreover, the applications of the model in heart disease research are endless.
“[This] model of ischemic heart disease, based on iPS CMs of human origin, can provide a useful platform for drug screening and further research on ischemic heart disease”, conclude the researchers.
