Okayama University


Okayama University Medical Research Updates (OU-MRU) Vol.83

November 12, 2020

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

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.

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
Model of Ischemic Heart Disease and Video-Based Comparison of Cardiomyocyte Contraction Using hiPSC-Derived Cardiomyocytes

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.

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Okayama University Medical Research Updates (OU-MRU)
The whole volume : OU-MRU (1- )
Vol.1:Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2:Ensuring a cool recovery from cardiac arrest
Vol.3:Organ regeneration research leaps forward
Vol.4:Cardiac mechanosensitive integrator
Vol.5:Cell injections get to the heart of congenital defects
Vol.6:Fourth key molecule identified in bone development
Vol.7:Anticancer virus solution provides an alternative to surgery
Vol.8:Light-responsive dye stimulates sight in genetically blind patients
Vol.9:Diabetes drug helps towards immunity against cancer
Vol.10:Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11:Compound-protein combination shows promise for arthritis treatment
Vol.12:Molecular features of the circadian clock system in fruit flies
Vol.13:Peptide directs artificial tissue growth
Vol.14:Simplified boron compound may treat brain tumours
Vol.15:Metamaterial absorbers for infrared inspection technologies
Vol.16:Epigenetics research traces how crickets restore lost limbs
Vol.17:Cell research shows pathway for suppressing hepatitis B virus
Vol.18:Therapeutic protein targets liver disease
Vol.19:Study links signalling protein to osteoarthritis
Vol.20:Lack of enzyme promotes fatty liver disease in thin patients
Vol.21:Combined gene transduction and light therapy targets gastric cancer
Vol.22:Medical supportive device for hemodialysis catheter puncture
Vol.23:Development of low cost oral inactivated vaccines for dysentery
Vol.24:Sticky molecules to tackle obesity and diabetes
Vol.25:Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26:Protein for preventing heart failure
Vol.27:Keeping cells in shape to fight sepsis
Vol.28:Viral-based therapy for bone cancer
Vol.29:Photoreactive compound allows protein synthesis control with light
Vol.30:Cancer stem cells’ role in tumor growth revealed
Vol.31:Prevention of RNA virus replication
Vol.32:Enzyme target for slowing bladder cancer invasion
Vol.33:Attacking tumors from the inside
Vol.34:Novel mouse model for studying pancreatic cancer
Vol.35:Potential cause of Lafora disease revealed
Vol.36:Overloading of protein localization triggers cellular defects
Vol.37:Protein dosage compensation mechanism unravelled
Vol.38:Bioengineered tooth restoration in a large mammal
Vol.39:Successful test of retinal prosthesis implanted in rats
Vol.40:Antibodies prolong seizure latency in epileptic mice
Vol.41:Inorganic biomaterials for soft-tissue adhesion
Vol.42:Potential drug for treating chronic pain with few side effects
Vol.43:Potential origin of cancer-associated cells revealed
Vol.44:Protection from plant extracts
Vol.45:Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46:New method for suppressing lung cancer oncogene
Vol.47:Candidate genes for eye misalignment identified
Vol.48:Nanotechnology-based approach to cancer virotherapy
Vol.49:Cell membrane as material for bone formation
Vol.50:Iron removal as a potential cancer therapy
Vol.51:Potential of 3D nanoenvironments for experimental cancer
Vol.52:A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53:Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54:Measuring ion concentration in solutions for clinical and environmental research
Vol.55:Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56:New device for assisting accurate hemodialysis catheter placement
Vol.57:Possible link between excess chewing muscle activity and dental disease
Vol.58:Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59:Role of commensal flora in periodontal immune response investigated
Vol.60:Role of commensal microbiota in bone remodeling
Vol.61:Mechanical stress affects normal bone development
Vol.62:3D tissue model offers insights into treating pancreatic cancer
Vol.63:Promising biomarker for vascular disease relapse revealed
Vol.64:Inflammation in the brain enhances the side-effects of hypnotic medication
Vol.65:Game changer: How do bacteria play Tag ?
Vol.66:Is too much protein a bad thing?
Vol.67:Technology to rapidly detect cancer markers for cancer diagnosis
Vol.68:Improving the diagnosis of pancreatic cancer
Vol.69:Early gastric cancer endoscopic diagnosis system using artificial intelligence
Vol.70:Prosthetics for Retinal Stimulation
Vol.71:The nervous system can contribute to breast cancer progression
Vol.72:Synthetic compound provides fast screening for potential drugs
Vol.73:Primary intraocular lymphoma does not always spread to the central nervous system
Vol.74:Rising from the ashes—dead brain cells can be regenerated after traumatic injury
Vol.75:More than just daily supplements — herbal medicines can treat stomach disorders
Vol.76:The molecular pathogenesis of muscular dystrophy-associated cardiomyopathy
Vol.77:Green leafy vegetables contain a compound which can fight cancer cells
Vol.78:Disrupting blood supply to tumors as a new strategy to treat oral cancer
Vol.79:Novel blood-based markers to detect Alzheimer’s disease
Vol.80:A novel 3D cell culture model sheds light on the mechanisms driving fibrosis in pancreatic cancer
Vol.81:Innovative method for determining carcinogenicity of chemicals using iPS cells
Vol.82:Making memories — the workings of a neuron revealed