1: Reproducing Human Heart Failure Using Human iPS Cells in a Culture Dish and Elucidating the Mechanism of New Therapeutic Effects of the Diabetes Drug SGLT2 Inhibitor / 2: Elucidating Why Osteosarcoma Frequently Occurs Near the Knees During Adolescence
Science of the Month - August 2026
1: Reproducing Human Heart Failure Using Human iPS Cells in a Culture Dish and Elucidating the Mechanism of New Therapeutic Effects of the Diabetes Drug SGLT2 Inhibitor
Tani H, Haga K, Moriwaki T, Bang U, Fujii S, Sekiguchi D, Yamamoto Y, Momoi K, Ohno M, Nakamura M, Umei TC, Morita-Umei Y, Soma Y, Kishino Y, Sano M, Fukuda K, Hotta A, Ieda M, Tohyama S.
In recent years, the number of heart failure patients has been increasing globally, a phenomenon referred to as the "heart failure pandemic." In particular, heart failure with preserved ejection fraction (HFpEF)—where diastolic function decreases despite the heart's contractile function being maintained—is steadily increasing in patient numbers due to the aging population. Meanwhile, effective treatments for HFpEF have remained largely unestablished. In this study, we succeeded in reproducing the pathology of HFpEF in a culture dish using three-dimensional myocardial tissue that combines cardiomyocytes, epicardial cells, vascular endothelial cells, and macrophages derived from human iPS cells. Specifically, by adding high fatty acids and a NOS inhibitor that blocks the production of nitric oxide (NO) to the cultured tissue, we reproduced the pathology unique to HFpEF, where only the diastolic function (the heart's ability to relax) decreases while the contractile function is maintained. This model exhibited characteristics seen in HFpEF patients, such as elevated BNP, fibrosis, abnormal calcium dynamics, and mitochondrial dysfunction. Furthermore, after administering multiple heart failure drugs to this model, we found that only SGLT2 inhibitors improved the decline in diastolic function. The mechanism of action suggested that it contributes to the improvement of inflammation and myocardial damage by restoring eNOS-NO-cGMP-PKG signaling in vascular endothelial cells and reducing intracellular Na⁺ and Ca²⁺ overload. The human-derived HFpEF model established in this study is expected to serve as a research foundation that will contribute to further research developments, including not only the elucidation of pathology and applications in aging research but also the development of new therapeutic drugs, evaluation of drug efficacy, and personalized medicine for individual patients.
(Hidenori Tani, Fujita Health University Tokyo Advanced Medical Research Center)
2: Elucidating Why Osteosarcoma Frequently Occurs Near the Knees During Adolescence
Nature Communications.
Masato Saito, Fumie Nakasuka, Nao Sankoda, Yihan Wang, Jumpei Taguchi, Sho Ohta, Yosuke Yamada, Manabu Ozawa, Satoko Sakurai, Atsushi Kondo, Tetsuo Ushiku, Robert Nakayama, Masaya Nakamura, Hiroshi Takayanagi, Atsushi Shibata, Takuya Yamamoto & Yasuhiro Yamada
Osteosarcoma occurs most frequently in children and adolescents, particularly at the metaphysis of long bones where growth is most active. However, why it tends to occur at the "metaphysis" during the "growth period" has not been sufficiently understood until now.
In this study, we conducted a detailed analysis of osteoblasts, the cells that form bone during the growth period. The results revealed that in the metaphysis during the growth period, a signal called Indian hedgehog (IHH) secreted from chondrocytes in the growth plate acts as an "accelerator" to promote the proliferation of immature osteoblasts. On the other hand, since active cell proliferation puts a load on DNA, a "brake" called the DNA damage response was functioning to suppress abnormal proliferation. Furthermore, activating c-Myc, which is often abnormal in osteosarcoma, accelerated cell proliferation, but tumorigenesis was transiently suppressed as long as the "brake" was functioning. However, when p53 function was lost simultaneously with c-Myc activation, this defense mechanism collapsed, and sustained neoplastic proliferation led to a high incidence of osteosarcoma.
This study clarified that the disruption of the balance between the "growth accelerator" and the "brake that prevents canceration," both of which are inherently present in growing bone, leads to the development of osteosarcoma.
(Robert Nakayama and Masato Saito, Department of Orthopedic Surgery)
Other Published Papers
1）Genetic and clinical characteristics of cranial nerve schwannoma harboring SH3PXD2A-HTRA1 fusion gene.
Acta Neuropathologica.
Sogano J, Tamura R, Yo M, Nakamura K, Fukada I, Ueno T, Hino U, Tomioka A, Karatsu K, Nagao A, Ueda R, Nishihara H, Toda M.
2）Cultured Human Corneal Endothelial Cell Injection for Endothelial Graft Failure After DSAEK
JAMA Ophthalmology.
Rintaro Ogino 1, Mariko Shirane 1, Taiyo Shijo 1, Osama Ibrahim 1, Yukari Yagi-Yaguchi 1, Daisuke Tomida 1, Takefumi Yamaguchi