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Journal of Clinical and

                                                                 Translational Research




                                        REVIEW ARTICLE
                                        The role of large language models in induced

                                        pluripotent stem cell-derived cardiomyocytes
                                        research and clinical translation



                                        Dhienda C. Shahannaz 1,2  , Tadahisa Sugiura * , and Brandon E. Ferrell 2
                                                                               2
                                        1 Department of Medicine, Medical Education and Research Institute, Faculty of Medicine, Universitas
                                        Indonesia, Jakarta, Indonesia
                                        2 Department of Cardiothoracic and Vascular Surgery, Montefiore Medical Center, Albert Einstein
                                        College of Medicine, Bronx, New York, United States of America
                                        (This article belongs to the  Special Issue: Exploring the Potential of Large Language Models
                                        (ChatGPT) in Cardiovascular Disease Management)




                                        Abstract

                                        Background: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are
                                        redefining cardiovascular regenerative medicine, yet challenges in differentiation
                                        fidelity, functional maturation, and scalable production restrain their full clinical
                                        potential. Aim: This review evaluates the pioneering integration of large language
            *Corresponding author:      models (LLMs)—including GPT-4, BioGPT, and BioMedLM—into iPSC-CM research
            Tadahisa Sugiura            and translational therapeutics, with a focus on advancing precision, efficiency, and
            (tsugiura@montefiore.org)   patient-specific care. Methods: Structured searches across biomedical and artificial
            Citation: Shahannaz DC,     intelligence-focused databases were conducted to map how LLMs augment literature
            Sugiura T, Ferrell BE. The role of   mining, experimental design, multi-omics integration, and clinical translation,
            large language models in induced   including personalized therapy prediction and drug safety assessment. Results: LLMs
            pluripotent stem cell-derived
            cardiomyocytes research and   demonstrably surpass traditional tools in identifying gene-phenotype links, refining
            clinical translation. J Clin Transl   clustered regularly interspaced short palindromic repeats-based differentiation
            Res. 2025;11(5):4-28.       protocols, and merging patient-level datasets with iPSC-CM outputs. Limitations
            doi: 10.36922/JCTR025230026
                                        include model interpretability, reproducibility across genetically diverse populations,
            Received: June 3, 2025      and ethical considerations regarding data privacy and bias.  Conclusion:  Despite
            Revised: July 20, 2025      these barriers, early translational applications demonstrate that LLMs can accelerate
                                        hypothesis generation, optimize laboratory-to-clinic pipelines, and enable high-
            Accepted: August 7, 2025
                                        fidelity, patient-specific cardiomyocyte modeling.  Relevance for patients:  The
            Published online: September 2,   synergy of LLM intelligence and iPSC-CM biology has the potential to deliver safer,
            2025
                                        more  effective,  and  deeply  personalized  regenerative  cardiac  therapies—moving
            Copyright: 2025 Author(s).   the field closer to truly bespoke heart repair.
            This is an open-access article
            distributed under the terms of the
            Creative Commons AttributionNon-
            Commercial 4.0 International (CC   Keywords: Artificial intelligence; Large language models; Biomedical natural language
            BY-NC 4.0), which permits all   programs; Induced pluripotent stem cells; Cardiac regenerative medicine
            non-commercial use, distribution,
            and reproduction in any medium,
            provided the original work is
            properly cited.             1. Introduction
            Publisher’s Note: AccScience
            Publishing remains neutral with   Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide,
                                                                                                             1
            regard to jurisdictional claims in
            published maps and institutional   necessitating continuous advancements in therapeutic strategies. According to the
                                                                                                2
            affiliations.               World Health Organization, CVDs account for 32% of global deaths,  with Indonesia
            Volume 11 Issue 5 (2025)                        4                          doi: 10.36922/JCTR025230026
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