TEACHER
Date:24 July
Time:16:20-16:50 (GMT+8)
In recent years, induced pluripotent stem cells (iPSCs) have made remarkable progress, with significant achievements reported in both basic and clinical research worldwide. In this presentation, I will begin by introducing several major advances in Japan’s iPSC-based clinical applications, including ongoing regenerative therapies and translational research supported by national initiatives.
Our laboratory focuses on integrating micro- and nanofabrication technologies with stem cell biology to design highly defined microenvironments and nanosurfaces that mimic in vivo conditions. These engineered systems enable precise regulation of iPSC behavior—including self-renewal, differentiation, and functional maturation. Among our key innovations is the development of gelatin-based nanofiber scaffolds, which support large-scale expansion of iPSCs while maintaining their pluripotency. In addition, these nanofibers enable label-free cell separation based on differential adhesion and morphology, offering a simple and scalable strategy for enriching specific cell subtypes.
Regarding downstream applications of iPSCs, our focus has been on iPSC-derived cardiomyocytes. A common challenge in the field is the immaturity of iPSC-derived cardiomyocytes, which can limit their utility for drug assessment. To address this, we developed a traveling wave-based cardiac maturation platform that significantly enhances the electrophysiological and contractile properties of iPSC-derived cardiomyocytes. When applied to drug testing, these mature cardiomyocytes exhibited more accurate responses compared to those in the control group.
To advance the therapeutic application of iPSC-derived cardiomyocytes in heart repair, we engineered fibrous scaffolds that support the formation of well-organized cardiac tissue-like constructs (CTLCs), mimicking the three-dimensional and anisotropic organization of cardiac cells in vivo. Building on this, we developed a multilayered fibrous scaffold with dynamic perfusion capability, enabling the single-step seeding of approximately 20 million hiPSC-derived cardiomyocytes to generate a 1 mm-thick, viable cardiac tissue. To further enhance structural organization and functional maturation, the constructs incorporated aligned fibers, pro-angiogenic factors, and co-culture with mesenchymal stem cells (MSCs). These engineered 3D cardiac tissues exhibited enhanced contractility, increased cytokine secretion, and significantly improved functional recovery with reduced fibrosis in a myocardial infarction model. These findings underscore the importance of precisely evaluating hiPSC-CM dosage in clinical applications and demonstrate the high potential of engineered cardiac tissues for future regenerative therapies.