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Updated: Dec 11, 2025
Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
Published on: February 12, 2021
Development of Cardiac Regenerative Medicine Using Human iPS Cell-derived Cardiomyocytes
Jun Fujita1,2
1Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
Insights
Cardiac regenerative therapy using human induced pluripotent stem cells (hiPSCs) shows promise for heart failure treatment. Clinical-grade cardiomyocytes and novel transplantation methods are advancing toward large animal models and potential human application.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Stem Cell Therapy
Background:
- Heart failure is a global health crisis with limited treatment options, making cardiac transplantation the last resort.
- Donor shortages critically limit cardiac transplantation, highlighting the need for alternative therapies like cardiac regenerative medicine.
- Human induced pluripotent stem cells (hiPSCs) offer a renewable source for generating cardiomyocytes for therapeutic applications.
Purpose of the Study:
- To review the current status and future challenges of cardiac regenerative therapy using hiPSC-derived cardiomyocytes.
- To discuss advancements in generating clinical-grade cardiomyocytes and developing effective transplantation strategies.
- To evaluate the progress toward clinical application, including large animal studies and remaining hurdles.
Main Methods:
- Generation and purification of clinical-grade cardiomyocytes from hiPSCs.
- Development of metabolic purification and mass-scale culture systems for cardiomyocytes.
- Engineering of a cardiac transplantation device for uniform spheroid injection into myocardial tissue.
- Utilizing large animal models (swine) to test transplantation efficacy and safety.
Main Results:
- Established methods for producing pure, clinical-grade hiPSC-derived cardiomyocytes.
- Development of cardiac spheroids to improve cell engraftment compared to single cells.
- Successful uniform injection of cardiac spheroids into swine myocardial layers using a novel transplantation device.
- Demonstrated feasibility of hiPSC-cardiomyocyte transplantation in a large animal model.
Conclusions:
- Cardiac regenerative therapy using hiPSC-derived cardiomyocytes is progressing towards clinical application.
- Novel transplantation devices and spheroid formation enhance cell delivery and engraftment.
- Further research is needed to address immunological rejection and potential arrhythmias for safe and effective therapy.
Abstract:
Heart failure is a life-threatening disease prevalent worldwide. Cardiac transplantation is the last resort for patients with severe heart failure, but donor shortages represent a critical issue. Cardiac regenerative therapy is beneficial, but it is currently unsuitable as a substitute for cardiac transplantation. Human induced pluripotent stem cells (hiPSCs) are excellent sources for the generation of terminally differentiated cells. The preparation of a large number of pure cardiomyocytes (CMs) is the major premise for translational studies. To control the quality of the generated CMs, an efficient differentiation method, purification strategy, and mass-scale culture must be developed. Metabolic purification and large-scale culture systems have been established, and pure hiPSC-derived CMs of clinical grade are now available for translational research. The most critical challenge in cell therapy is the engraftment of transplanted cells. To overcome the low engraftment ratio of single CMs, aggregations of CMs are developed as cardiac spheroids. A cardiac transplantation device with domed tips and lateral holes has been developed for the transplantation of cardiac spheroids. Large animal models are necessary as the next step in the process toward clinical application. The transplant device has successfully been used to inject cardiac spheroids uniformly into myocardial layers in swine, and this approach is progressing toward clinical use. Remaining issues include immunological rejection and arrhythmia, which will require further investigation to establish safe and effective transplantation. This review summarizes the present status and future challenges of cardiac regenerative therapies.
Related Concept Videos
01:22iPS Cell Differentiation
01:13Induced Pluripotent Stem Cells