Related Experiment Video
Updated: Nov 15, 2025
High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers
Published on: March 24, 2023
Scaffold-Mediated Developmental Effects on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Are Preserved
Jun Li1, Jong-Kook Lee1,2, Keiko Miwa2,3
1Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Insights
Topographic substrates, particularly aligned fibers, promote human induced pluripotent stem-cardiomyocyte maturation. While physical cues are crucial for morphology and function, molecular development persists even after scaffold removal, aiding regenerative therapy applications.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Biomaterials Science
Background:
- Human induced pluripotent stem cells (hiPS) are vital for regenerative medicine and disease modeling.
- Advancements have improved hiPS-cardiomyocyte (hiPS-CM) purity, but immaturity hinders clinical use.
- Understanding factors influencing hiPS-CM maturation is critical for therapeutic applications.
Purpose of the Study:
- To investigate the impact of topographic substrates on hiPS-CM maturation.
- To assess the reversibility of substrate-induced maturation effects.
- To explore the potential for creating biomimetic cardiac tissue.
Main Methods:
- hiPS-CMs were cultured on three substrates: random fiber, aligned fiber, and flat non-scaffold.
- Morphological, electrophysiological, and gene expression analyses were performed.
- Cells were subsequently transferred to a flat substrate to evaluate reversibility.
Main Results:
- Aligned fiber substrates promoted hiPS-CM maturation, evidenced by elongated shape, shorter action potential duration, and faster conduction velocity.
- Cardiac gene expression was significantly elevated on aligned patterns.
- While morphological and functional improvements diminished after scaffold removal, molecular features of maturation were retained.
Conclusions:
- Anisotropic fiber substrates can rapidly induce biomimetic, oriented cardiac tissue.
- Substrate-dependent maturation of hiPS-CMs shows partial reversibility in morphology and electrophysiology.
- Molecular maturation features persist independently of the scaffold, suggesting long-term developmental potential.
Abstract:
Human induced pluripotent stem (hiPS) cells have been used as a cell source for regenerative therapy and disease modeling. The purity of hiPS-cardiomyocytes (hiPS-CMs) has markedly improved with advancements in cell culture and differentiation protocols. However, the morphological features and molecular properties of the relatively immature cells are still unclear, which has hampered their clinical application. The aim of the present study was to investigate the extent to which topographic substrates actively influence hiPS-CMs. hiPS-CMs were seeded on randomized oriented fiber substrate (random), anisotropic aligned fiber substrate (align), and flat non-scaffold substrate (flat). After culturing for one week, the hiPS-CMs on the aligned patterns showed more mature-like properties, including elongated rod shape, shorter duration of action potential, accelerated conduction velocity, and elevated cardiac gene expression. Subsequently, to determine whether this development was irreversible or was altered after withdrawal of the structural support, the hiPS-CMs were harvested from the three different patterns and reseeded on the non-scaffold (flat) pattern. After culturing for one more week, the improvements in morphological and functional properties diminished, although hiPS-CMs pre-cultured on the aligned pattern retained the molecular features of development, which were even more significant as compared to that observed during the pre-culture stage. Our results suggested that the anisotropic fiber substrate can induce the formation of geometrical mimic-oriented heart tissue in a short time. Although the morphological and electrophysiological properties of hiPS-CMs obtained via facilitated maturation somehow rely on the existence of an exterior scaffold, the molecular developmental features were preserved even in the absence of the external support, which might persist throughout hiPS-CM development.
More Related Videos
09:23Generation, High-Throughput Screening, and Biobanking of Human-Induced Pluripotent Stem Cell-Derived Cardiac Spheroids
Published on: March 10, 2023
11:13Electrophysiological Analysis of human Pluripotent Stem Cell-derived Cardiomyocytes hPSC-CMs Using Multi-electrode Arrays MEAs
Published on: May 12, 2017