Elsevier BV Acta Medica Okayama 2589-0042 29 4 2026 Human iPSC cardiomyocyte patch transplantation modifies extracellular matrix and fibroblast behavior after myocardial infarction 115341 EN Kosuke Torigata Cuorips Inc. Ryohei Matsuura Max Planck Institute for Heart and Lung Research, Laboratory for Cell Polarity and Organogenesis Fumiya Nagatomo Department of Mechanical Engineering, School of Engineering, The University of Tokyo Moe Thiha Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Takao Hikita Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Hiroko Iseoka Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine Hiromitsu Takagi Daiichi Sankyo Co., Ltd. Uichi Koshimizu Daiichi Sankyo Co., Ltd. Hiroki Sakakima Department of Mechanical Engineering, School of Engineering, The University of Tokyo Satoshi Izumi Department of Mechanical Engineering, School of Engineering, The University of Tokyo Asuka Hatano Department of Mechanical Engineering, School of Engineering, The University of Tokyo Thomas Braun MaxPlanck Institute for Heart and Lung Research, Department of Cardiac Development and Remodeling Yoshiki Sawa Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine Shigeru Miyagawa Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine Masanori Nakayama Department of Pathophysiology and Drug Discovery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Myocardial infarction (MI) followed by chronic heart failure is the main cause of mortality of heart diseases. Although reparative cell transplantation therapies with pluripotent stem cell-derived cardiomyocytes (CMs) represent a promising therapeutic strategy, molecular mechanisms of the therapy remain elusive. Here, we show that transplantation of the human induced pluripotent stem cell (hiPSC)-derived CM patch onto the damaged heart after MI increases the ratio of collagen type I against collagen type III to modulate alignment of the collagen fibers at the infarcted zone. As a result, tissue elasticity of the heart is improved, and fibrosis at the remote zone is reduced. Mechanistically, we find that hiPSC-derived CM patches secrete TGF-ƒÀ1, directly inducing collagen type I production in fibroblasts but not collagen type III. Our results suggest the direct effect of the transplanted CM patch on the cardiac fibroblasts to improve elasticity of the damaged heart, resulting in functional recovery after MI. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-0042 29 4 2026 Multifaceted role of POU5F1P1 in regulating its parental stem cell gene, POU5F1 115137 EN Kyohei Irie Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuko Kosaka Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuhiko Mizuno Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Omae Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshimasa Nakatani Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Sandi Myat Noe Oo Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayano Kawaguchi Department of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The human-specific retrogene POU5F1P1 (OCT4-Pseudogene1; OCT4-PG1), derived from stem cell factor POU5F1 (OCT4A), is predicted to encode an OCT4A-like protein; however, its function remains unclear. This study investigated OCT4-PG1 expression, translational control, and its role in endometrial cancer and stem cell regulation. Quantitative analyses revealed that elevated OCT4A, but not OCT4-PG1, expression correlated with clinical risk factors associated with poor prognosis in patients with endometrial cancer. OCT4-PG1 is under strong translational suppression mediated by its untranslated region and does not function as a protein under normal conditions. Instead, it acts as a non-coding RNA that suppresses OCT4A translation. Structural analyses showed that a single amino acid deletion (Gln259) destabilizes the OCT4-PG1 protein, thereby preventing its tumorigenic and transcriptional functions. Nevertheless, OCT4-PG1 forms heterodimers with OCT4A or SOX2, enhancing the regulatory activity of OCT4A. These findings highlight the regulatory role of pseudogenes in cancer and stem cell biology, with implications for therapies targeting OCT4A-related pathways. No potential conflict of interest relevant to this article was reported.