Induced Pluripotent Stem Cell-Derived Cardiomyocytes: From Regulatory Status to Clinical Translation

Cardiovascular diseases, considered the deadliest worldwide by the World Health Organization (WHO), lack effective therapies for regenerating cardiomyocytes. With their self-renewal and pluripotency capabilities, stem cell therapies are increasingly used in precision medicine. Induced pluripotent stem cells (iPSCs) are a promising alternative to embryonic stem cells. Good Manufacturing Practice (GMP) principles are not yet adapted for large-scale production of iPSCs. Additionally, the quality risk for iPSC products may not always be possible to eliminate, potentially jeopardizing the health of patients. This review aims to identify critical quality attributes (CQAs) for iPSC-derived cardiomyocytes (iPSC-CMs) for the development of cardiovascular therapy to ensure compliance with regulations and safety for patients. To attain these goals, the literature review was conducted with articles related to iPSCs and iPSC-CM therapies, legislation, and regulatory guidelines of the European Medicines Agency (EMA), Food and Drug Administration (FDA), and Pharmaceuticals and Medical Devices Agency (PMDA). In conclusion, additional regulations and guidelines are needed to monitor differentiation, maturation, and tumorigenicity. GMP-compliant cell banks and fast-track approval systems may increase accessibility for patients. Impact statement By identifying critical quality attributes for induced pluripotent stem cell (iPSC)-derived cardiomyocyte (iPSC-CM) therapy, this work has the potential to develop the field of regenerative medicine. Developing a high quality and safe product that meets Good Manufacturing Practice (GMP) principles and applicable regulations is crucial for the success of cell therapies. Additionally, the implementation of GMP-compliant cell banks and fast-track approval systems can significantly improve patient access to these treatments. Ultimately, this could lead to more effective treatments for cardiovascular disease, improving patient outcomes and quality of life. This work represents a significant step forward in the development of regenerative medicine and has the potential to significantly impact the field.