The role of large language models in induced pluripotent stem cell-derived cardiomyocytes research and clinical translation
Dhienda C. Shahannaz , Tadahisa Sugiura , Brandon E. Ferrell
Journal of Clinical and Translational Research ›› 2025, Vol. 11 ›› Issue (5) : 4 -28.
The role of large language models in induced pluripotent stem cell-derived cardiomyocytes research and clinical translation
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 models (LLMs)—including GPT-4, BioGPT, and BioMedLM—into iPSC-CM research and translational therapeutics, with a focus on advancing precision, efficiency, and patient-specific care. Methods: Structured searches across biomedical and artificial intelligence-focused databases were conducted to map how LLMs augment literature mining, experimental design, multi-omics integration, and clinical translation, including personalized therapy prediction and drug safety assessment. Results: LLMs demonstrably surpass traditional tools in identifying gene-phenotype links, refining clustered regularly interspaced short palindromic repeats-based differentiation protocols, and merging patient-level datasets with iPSC-CM outputs. Limitations include model interpretability, reproducibility across genetically diverse populations, and ethical considerations regarding data privacy and bias. Conclusion:Despite these barriers, early translational applications demonstrate that LLMs can accelerate hypothesis generation, optimize laboratory-to-clinic pipelines, and enable high-fidelity, patient-specific cardiomyocyte modeling. Relevance for patients: The synergy of LLM intelligence and iPSC-CM biology has the potential to deliver safer, more effective, and deeply personalized regenerative cardiac therapies—moving the field closer to truly bespoke heart repair.
Artificial intelligence / Large language models / Biomedical natural language programs / Induced pluripotent stem cells / Cardiac regenerative medicine
| [1] |
|
| [2] |
World Health Organization: WHO. Cardiovascular Diseases (CVDs); 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) [Last accessed on 2025 May 20]. |
| [3] |
|
| [4] |
|
| [5] |
|
| [6] |
|
| [7] |
|
| [8] |
|
| [9] |
World Heart Federation. CVD Prevention What we Do World Heart Federation. World Heart Federation; 2024. Available from: https://world-heart-federation.org/what-we-do/prevention/#:-:text=The%20majority%20of%20deaths%20due,regular%20exercise%20and%20avoiding%20tobacco [Last accessed on 2025 May 20]. |
| [10] |
|
| [11] |
|
| [12] |
|
| [13] |
|
| [14] |
|
| [15] |
|
| [16] |
|
| [17] |
|
| [18] |
|
| [19] |
|
| [20] |
|
| [21] |
|
| [22] |
|
| [23] |
|
| [24] |
|
| [25] |
|
| [26] |
|
| [27] |
|
| [28] |
|
| [29] |
|
| [30] |
|
| [31] |
|
| [32] |
|
| [33] |
|
| [34] |
|
| [35] |
|
| [36] |
|
| [37] |
|
| [38] |
|
| [39] |
|
| [40] |
|
| [41] |
|
| [42] |
|
| [43] |
|
| [44] |
|
| [45] |
Llm-Jp, |
| [46] |
|
| [47] |
|
| [48] |
|
| [49] |
|
| [50] |
|
| [51] |
|
| [52] |
|
| [53] |
|
| [54] |
|
| [55] |
|
| [56] |
|
| [57] |
|
| [58] |
|
| [59] |
|
| [60] |
|
| [61] |
|
| [62] |
|
| [63] |
|
| [64] |
|
| [65] |
|
| [66] |
|
| [67] |
|
| [68] |
|
| [69] |
|
| [70] |
|
| [71] |
|
| [72] |
|
| [73] |
|
| [74] |
|
| [75] |
|
| [76] |
|
| [77] |
|
| [78] |
|
| [79] |
|
| [80] |
|
| [81] |
|
| [82] |
|
| [83] |
|
| [84] |
|
| [85] |
Keio University. AI Model Developed by Brigham Researchers Could Help Screen for Heart Defect. Keio University; 2023. Available from: https://www.keio.ac.jp/en/press-releases/files/2023/11/7/231107-1.pdf [Last accessed on 2025 May 27. |
| [86] |
|
| [87] |
|
| [88] |
|
| [89] |
|
| [90] |
|
| [91] |
|
| [92] |
|
| [93] |
|
| [94] |
|
| [95] |
RIKEN-Max Planck Joint Research Center for Systems Chemical Biology. RIKEN. Available from: https://www.riken.jp/en/collab/research/riken_mpg/ [Last accessed on 2025 May 20]. |
| [96] |
|
| [97] |
|
| [98] |
|
| [99] |
|
| [100] |
|
| [101] |
|
| [102] |
|
| [103] |
|
| [104] |
|
| [105] |
|
| [106] |
|
| [107] |
|
| [108] |
|
| [109] |
|
| [110] |
|
| [111] |
|
| [112] |
|
| [113] |
|
| [114] |
|
| [115] |
|
| [116] |
|
| [117] |
|
| [118] |
|
| [119] |
|
| [120] |
|
| [121] |
|
| [122] |
|
| [123] |
|
| [124] |
|
| [125] |
|
| [126] |
|
| [127] |
|
| [128] |
|
| [129] |
|
| [130] |
|
| [131] |
|
| [132] |
|
| [133] |
|
| [134] |
|
| [135] |
|
| [136] |
|
| [137] |
|
| [138] |
|
| [139] |
|
| [140] |
|
| [141] |
|
| [142] |
|
| [143] |
|
| [144] |
|
| [145] |
|
| [146] |
|
| [147] |
|
| [148] |
|
| [149] |
|
| [150] |
|
| [151] |
Kim K, Doi A, Wen B, et al. Epigenetic memory in induced pluripotent stem cells. Nature. 2010;467(7313):285-290. doi: 10.1038/nature09342 |
| [152] |
|
| [153] |
|
| [154] |
|
| [155] |
|
| [156] |
|
| [157] |
|
| [158] |
|
| [159] |
|
| [160] |
|
| [161] |
|
| [162] |
|
| [163] |
|
| [164] |
|
| [165] |
|
| [166] |
|
| [167] |
|
/
| 〈 |
|
〉 |