Source: Okayama University (JAPAN), Public Relations Division
For immediate release: 12 November 2020
Okayama University research: Skipping a beat—a novel method to study heart attacks
(Okayama, 12 November) In a video-based study recently published in the Journal of Visualized Experiments (JoVE),
researchers at Okayama University use stem cells to create a model of
ischemic heart disease that closely replicates cardiac cells under
stress.
Ischemic heart disease often leads to heart attacks and is the leading
cause of death worldwide. The condition manifests when the heart muscle
does not receive adequate oxygen and eventually starts giving way.
Scientists rely on animal models such as rats and mice to study ischemic
heart disease. However, there are pronounced differences between the
rodent and human heart, creating the need for a more “humanized” model.
Now, a research team led by Research Associate Professor TAKAHASHI Ken
and Professor NARUSE Keiji at Okayama University has created such a
model using human stem cells.
Stem cells have the unique ability to grow into any kind of specialized
cell if given the right cocktail of growth factors. The team leveraged
this 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.
Related video
A video showcasing the experiments conducted in this study accompanies
the article. Research Associate Professor TAKAHASHI research team from
Okayama University depict a play-by-play of their newly developed
research protocol in this video. All steps, starting from maintenance of
the hiPSCs, followed by differentiation into cardiomyocytes, and the
subsequent induction of ischemia are portrayed. The team also provides
insights into measuring contractility along with a glimpse into the
successful simulation of ischemic heart disease within the
cardiomyocytes. This video will be especially useful for researchers in
the field looking to replicate this model of ischemic heart disease for
drug screening, genetic screening, or other research purposes.
The video can be accessed at: https://www.jove.com/t/61104/model-ischemic-heart-disease-video-based-comparison-cardiomyocyte
Background
Ischemic heart disease – Ischemic heart disease is a fatal condition
that stems from an inadequate blood supply to the heart muscles. The
most common cause of ischemic heart disease is a blockage of the
arteries supplying the walls of the heart due to blood clots or plaques.
The cardiomyocytes then start dying due to a lack of oxygen, with
patients often suffering heart attacks. Ischemic heart disease is the
leading cause of mortality worldwide, and accounts for 40% of heart
disease–related deaths in Japan. Thus, reliable and reproducible
clinical models to study this condition are instrumental in developing
prophylactic and therapeutic strategies.
Reference
Yun Liu, Yin Liang, Mengxue Wang, Chen Wang, Heng Wei, Keiji Naruse, Ken
Takahashi. Model of Ischemic Heart Disease and Video-Based Comparison
of Cardiomyocyte Contraction Using hiPSC-Derived Cardiomyocytes. Journal
of Visualized Experiments, (159), e61104, 2020.
DOI : 10.3791/61104
Correspondence to
Research Associate Professor TAKAHASHI Ken, Ph.D.
Department of Cardiovascular Physiology, Graduate
School of Medicine, Dentistry and Pharmaceutical
Sciences, Okayama University, Shikata-cho 2-5-1,
Okayama city, Okayama 700-8558, Japan
e-mail : takah-k2(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.
https://www.okayama-u.ac.jp/user/med/phy2/index.htm
https://ken-takahashi.net/
Further information
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