Modeling doxorubicin-induced-cardiotoxicity through breast cancer patient specific iPSC-derived heart organoid
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 u...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-10-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024147457 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846170246842417152 |
|---|---|
| author | Jiye Jang Hyewon Jung Jaekyun Jeong Junseok Jeon Kyungho Lee Hye Ryoun Jang Jeung-Whan Han Jaecheol Lee |
| author_facet | Jiye Jang Hyewon Jung Jaekyun Jeong Junseok Jeon Kyungho Lee Hye Ryoun Jang Jeung-Whan Han Jaecheol Lee |
| author_sort | Jiye Jang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8fac20a1d87d413fb8fb1e288ac1a3a6 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-8fac20a1d87d413fb8fb1e288ac1a3a62024-11-12T05:19:12ZengElsevierHeliyon2405-84402024-10-011020e38714Modeling doxorubicin-induced-cardiotoxicity through breast cancer patient specific iPSC-derived heart organoidJiye Jang0Hyewon Jung1Jaekyun Jeong2Junseok Jeon3Kyungho Lee4Hye Ryoun Jang5Jeung-Whan Han6Jaecheol Lee7Department 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 KoreaDepartment 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 KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Epigenome Dynamics Control Research Center (EDCRC), School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of KoreaDivision of Nephrology, Department of Medicine, Cell and Gene Therapy Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of KoreaDivision of Nephrology, Department of Medicine, Cell and Gene Therapy Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of KoreaDivision of Nephrology, Department of Medicine, Cell and Gene Therapy Institute, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea; Epigenome Dynamics Control Research Center (EDCRC), School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of KoreaDepartment 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.http://www.sciencedirect.com/science/article/pii/S2405844024147457Doxorubicin-induced-cardiotoxicityInduced pluripotent stem cellHeart organoidDisease modelingPredictive model |
| spellingShingle | Jiye Jang Hyewon Jung Jaekyun Jeong Junseok Jeon Kyungho Lee Hye Ryoun Jang Jeung-Whan Han Jaecheol Lee Modeling doxorubicin-induced-cardiotoxicity through breast cancer patient specific iPSC-derived heart organoid Heliyon Doxorubicin-induced-cardiotoxicity Induced pluripotent stem cell Heart organoid Disease modeling Predictive model |
| title | Modeling doxorubicin-induced-cardiotoxicity through breast cancer patient specific iPSC-derived heart organoid |
| title_full | Modeling doxorubicin-induced-cardiotoxicity through breast cancer patient specific iPSC-derived heart organoid |
| title_fullStr | Modeling doxorubicin-induced-cardiotoxicity through breast cancer patient specific iPSC-derived heart organoid |
| title_full_unstemmed | Modeling doxorubicin-induced-cardiotoxicity through breast cancer patient specific iPSC-derived heart organoid |
| title_short | Modeling doxorubicin-induced-cardiotoxicity through breast cancer patient specific iPSC-derived heart organoid |
| title_sort | modeling doxorubicin induced cardiotoxicity through breast cancer patient specific ipsc derived heart organoid |
| topic | Doxorubicin-induced-cardiotoxicity Induced pluripotent stem cell Heart organoid Disease modeling Predictive model |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024147457 |
| work_keys_str_mv | AT jiyejang modelingdoxorubicininducedcardiotoxicitythroughbreastcancerpatientspecificipscderivedheartorganoid AT hyewonjung modelingdoxorubicininducedcardiotoxicitythroughbreastcancerpatientspecificipscderivedheartorganoid AT jaekyunjeong modelingdoxorubicininducedcardiotoxicitythroughbreastcancerpatientspecificipscderivedheartorganoid AT junseokjeon modelingdoxorubicininducedcardiotoxicitythroughbreastcancerpatientspecificipscderivedheartorganoid AT kyungholee modelingdoxorubicininducedcardiotoxicitythroughbreastcancerpatientspecificipscderivedheartorganoid AT hyeryounjang modelingdoxorubicininducedcardiotoxicitythroughbreastcancerpatientspecificipscderivedheartorganoid AT jeungwhanhan modelingdoxorubicininducedcardiotoxicitythroughbreastcancerpatientspecificipscderivedheartorganoid AT jaecheollee modelingdoxorubicininducedcardiotoxicitythroughbreastcancerpatientspecificipscderivedheartorganoid |