A research team from Fujita Health University, Japan, engineered a lab-grown model of heart failure with preserved ejection fraction (HFpEF), where the heart’s relaxation function is impaired.
Human induced pluripotent stem cell-derived tissues were cultured in a medium with abundant fatty acids and L-NG-nitroarginine methyl ester. This model was used to study HFpEF’s underlying disease processes and treatment options. Among the current treatment options tested, the antidiabetic SGLT2 inhibitors showed improvement in relaxation function.
Scientists study the underlying causes of a disease or test new potential drugs in animal models or cells obtained from human biopsy specimens before clinical trials. However, disease models in animals do not mimic the actual human disease, and biopsy specimens are hard to access for research purposes. Lab-grown tissues, engineered from stem cells reprogrammed from human cells, called human induced pluripotent stem cells (hiPSCs), are fast emerging as a more reliable and accessible model in medical research.
A study led by Professor Shugo Tohyama and Senior Assistant Professor Hidenori Tani from the Department of Clinical Regenerative Medicine, Fujita Health University, Japan, has focused on developing robust lab models of cardiomyocytes (CMs), the heart muscle cells. Years of pioneering research have led to the development of high-quality CMs from hiPSCs in a petri dish.
“During efforts to adjust the concentrations of glucose and fatty acids in the culture medium to promote heart tissue maturation, we discovered that excessive fatty acids adversely affected the dilation capacity of the heart tissues,” explains Dr. Tani, the first author of the study, regarding this breakthrough. “Around the same time, a study reported that the administration of high levels of fatty acids and nitric oxide synthase (NOS) inhibitors in mice-induced heart failure (HF) with preserved ejection fraction (HFpEF), which led to the conception of this study.”
Fujita Health University
The study, which resulted in the development of human engineered heart tissue (hEHT) model of HFpEF, was made available online on July 16, 2026, and was published in Volume 33, Issue 8 of the journal Cell Stem Cell on August 6, 2026. Following its publication, the study was immediately selected as a featured paper in the Preview section of Cell Stem Cell, further highlighting the significance of these findings.
