Research Overview

Research

We aim to realize next-generation cardiovascular medicine based on human iPS cells and three-dimensional tissue engineering, with core strengths in regenerative medicine, disease modeling and drug discovery, and organoid maturation.

Core Areas

Three Core Research Areas

Building on human iPS cell and cardiac organoid technologies, we advance regenerative medicine, drug discovery, and organoid maturation in an integrated manner.

Regenerative Medicine

We develop transplantable cardiac tissues and vascularized constructs to establish new therapies for severe cardiovascular diseases.

Disease Modeling & Drug Discovery

Using disease models and heart-on-a-chip platforms, we investigate pathophysiology and evaluate drug efficacy and safety.

Organoid Maturation

We enhance physiological function through physical training approaches such as electrical and mechanical stimulation.

Research overview illustration
Regenerative Medicine

1. Regenerative Medicine

Our laboratory conducts a wide range of studies in regenerative medicine, with a particular focus on developing treatments for cardiac disease using iPS cells. We use multiple cardiovascular cell types derived from iPS cells, including cardiomyocytes, to explore new therapeutic strategies for myocardial infarction, heart failure, and related conditions.

In particular, we actively pursue organoid-based research grounded in tissue engineering approaches using iPS cells. By constructing organoids that recapitulate cardiac structure and function, we aim to elucidate mechanisms of cardiac regeneration and advance toward “true” regenerative medicine that restores myocardial function through tissue regeneration.

We also investigate the application of biomaterials to enhance therapeutic efficacy. These efforts are expected to support future clinical applications in cardiac regenerative medicine.

References

References

Kuroda Y, Iida J, Murata K, Hori Y, Kobiki J, Minatoya K, Masumoto H*. Transplantation of vascularized cardiac microtissue from human iPS cells improves impaired electrical conduction in a porcine myocardial injury model. JTCVS Open. In press.
Iida J, Kotani K, Murata K, Hakamada K, Maihemuti W, Mandai Y, Hiraoka Y, Minatoya K, Masumoto H*. Retention of locally injected human iPS cell-derived cardiomyocytes into the myocardium using hydrolyzed gelatin. Sci Rep. 2025;15:4635. doi:10.1038/s41598-025-87885-w.
Heima D, Takeda M, Tabata Y, Minatoya K, Yamashita JK*, Masumoto H*. Therapeutic potential of human induced pluripotent stem cell-derived cardiac tissue in an ischemic model with unloaded condition mimicking left ventricular assist device. J Thorac Cardiovasc Surg. 2024;168:e72-e88. doi:10.1016/j.jtcvs.2023.11.019.
Osada H, Kawatou M, Fujita D, Tabata Y, Minatoya K, Yamashita JK*, Masumoto H*. Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues. JTCVS Open. 2021;8:359-374. doi:10.1016/j.xjon.2021.09.038.
Ishigami M, Masumoto H*, Ikuno T, Aoki T, Kawatou M, Minakata K, Ikeda T, Sakata R, Yamashita JK*, Minatoya K. Human iPS cell-derived cardiac tissue sheets for functional restoration of infarcted porcine hearts. PLoS One. 2018;13:e0201650. doi:10.1371/journal.pone.0201650.
Nakane T, Masumoto H, Tinney JP, Yuan F, Kowalski WJ, Ye F, LeBlanc AJ, Sakata R, Yamashita JK, Keller BB*. Impact of Cell Composition and Geometry on Human Induced Pluripotent Stem Cells-Derived Engineered Cardiac Tissue. Sci Rep. 2017;7:45641. doi:10.1038/srep45641.
Masumoto H, Nakane T, Tinney JP, Yuan F, Ye F, Kowalski WJ, Minakata K, Sakata R, Yamashita JK, Keller BB*. The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages. Sci Rep. 2016;6:29933. doi:10.1038/srep29933.
A spontaneously beating cardiac organoid composed of multiple cardiac cell types generated from human iPS cells.
Transplantation into a rat myocardial infarction model
Human iPS cell-derived cardiac organoids transplanted into a rat myocardial infarction model. One month later, human myocardial tissue with a vascular network was regenerated in the rat heart. Red: human nuclear antigen; green: von Willebrand factor (vascular endothelial cells). (Collaborative work with the University of Louisville, USA.)
Disease Modeling / Drug Discovery

2. Disease Modeling and Drug Discovery

We use iPS cells and organoid technologies to recreate a variety of disease models and explore new opportunities for drug discovery. In particular, we focus on cardiovascular disease models to better understand disease mechanisms and develop novel therapeutic strategies.

We are also advancing drug discovery research using Organ-on-a-Chip (OoC) technology. By constructing heart-on-a-chip systems that mimic cardiac and vascular structures, we analyze intercellular interactions and drug responses under disease conditions.

This technology is also expected to serve as an alternative to animal experimentation and to facilitate the development of more human-relevant therapeutic approaches. Our work in disease modeling and drug discovery aims to deepen mechanistic understanding and enable innovative treatments through both regenerative medicine and pharmacological research.

References

References

Murata K, Makino A, Tomonaga K*, Masumoto H*. Predicted risk of heart failure pandemic due to persistent SARS-CoV-2 infection using a three-dimensional cardiac model. iScience. 2023;27:108641. doi:10.1016/j.isci.2023.108641. (Cover image)
Abulaiti M, Yalikun Y, Murata K, Sato A, Sami MM, Sasaki Y, Fujiwara Y, Minatoya K, Shiba Y, Tanaka Y, Masumoto H*. Establishment of a heart-on-a-chip microdevice based on human iPS cells for the evaluation of human heart tissue function. Sci Rep. 2020;10:19201. doi:10.1038/s41598-020-76062-w.
Kawatou M, Masumoto H, Fukushima H, Morinaga G, Sakata R, Ashihara T, Yamashita JK*. Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue. Nat Commun. 2017;8:1078. doi:10.1038/s41467-017-01125-y.
iScience 2023 cover image
Artwork associated with the paper showing the potential risk of heart failure caused by persistent SARS-CoV-2 infection using human iPS cell-derived cardiac organoids (Murata, iScience, 2023). Selected as the cover image for iScience, Volume 27, Issue 2 (February 2024). © Hayanon Science Manga Studio (2024)
Organoid Maturation

3. Organoid Maturation

We aim to promote the maturation of iPS cell-derived organoids so that they more closely approximate physiological tissue states. Organoids are three-dimensional cellular assemblies that self-organize to mimic the structure of a specific organ, but insufficient maturation remains a major challenge for both regenerative medicine and disease modeling.

To address this, we apply “physical training” approaches, including mechanical and electrical stimulation. In cardiac organoids, mechanical loading that promotes contractile activity is used to enhance the maturation of cardiomyocyte function. These stimuli strengthen contractility and electrophysiological activity, enabling the generation of organoids with more realistic cardiac properties.

We also investigate the molecular mechanisms that govern organoid maturation and explore ways to regulate these processes. For example, we study activation of specific transcription factors and intercellular signaling pathways that promote maturation. Improving cell–cell interactions within organoids is another important strategy for enhancing maturity.

To evaluate mature organoids, we measure contractile force, electrophysiological activity, and metabolic function. Based on these assessments, we seek to identify the most effective stimuli and culture conditions that maximize physiological performance.

Our work on organoid maturation is expected to make major contributions to improving the precision of regenerative therapies and the reproducibility of disease models, ultimately opening the way toward more practical clinical applications.

References

References

Maihemuti W, Murata K, Abulaiti M, Minatoya K, Masumoto H*. Simultaneous electro-dynamic stimulation accelerates maturation of engineered cardiac tissues generated by human iPS cells. Biochem Biophys Res Commun. 2024;733:150605. doi:10.1016/j.bbrc.2024.150605.