Modeling doxorubicin-induced-cardiotoxicity through breast cancer patient specific iPSC-derived heart organoid
Jiye Jang,
Hyewon Jung,
Jaekyun Jeong,
Junseok Jeon,
Kyungho Lee,
Hye Ryoun Jang,
Jeung-Whan Han,
Jaecheol Lee
Affiliations
Jiye Jang
Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Epigenome Dynamics Control Research Center (EDCRC), School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea
Hyewon Jung
Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Epigenome Dynamics Control Research Center (EDCRC), School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea
Jaekyun Jeong
School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Epigenome Dynamics Control Research Center (EDCRC), School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea
Junseok Jeon
Division of Nephrology, Department of Medicine, Cell and Gene Therapy Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
Kyungho Lee
Division of Nephrology, Department of Medicine, Cell and Gene Therapy Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
Hye Ryoun Jang
Division of Nephrology, Department of Medicine, Cell and Gene Therapy Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
Jeung-Whan Han
School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Epigenome Dynamics Control Research Center (EDCRC), School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea
Jaecheol Lee
Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Epigenome Dynamics Control Research Center (EDCRC), School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, 16419, Republic of Korea; Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Corresponding author. Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Heart organoid (HO) technology has successfully overcome the limitations of two-dimensional (2D) disease modeling and drug testing, thereby emerging as a valuable tool in drug discovery for assessing toxicity and efficacy. However, its ability to distinguish drug responses among individuals remain unclear, which is crucial for developing predictive models. We addressed this gap by comparing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with human induced pluripotent stem cell-derived heart organoids (hiPSC-HOs) in the context of doxorubicin-induced cardiotoxicity (DIC). For this study, we utilized hiPSCs generated from breast cancer patients who had previously been treated with doxorubicin. By comparing groups with and without DIC, we examined various parameters, including cell viability, mRNA expression, protein expression and electrophysiological variations. The results of our analysis revealed significant differences between these groups, providing insights into hiPSC-HOs as a potential platform for testing differences in drug responses among patients.
