Review
Pharmacology & Pharmacy
Wendy Keung, Yiu-Fai Cheung
Summary: Chemotherapies for cancer treatment often lead to severe side effects, with cardiotoxicity being a notable concern. Identifying risk factors and understanding the underlying mechanisms of cardiotoxicity are essential for improving clinical outcomes. Human induced pluripotent stem cell technology offers a promising platform for validating risk factors and advancing personalized medicine.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Cell Biology
Mo-Fan Huang, Lon Kai Pang, Yi-Hung Chen, Ruiying Zhao, Dung-Fang Lee
Summary: The field of cancer treatment has advanced, but the adverse effects of chemotherapy on the cardiovascular system require further research for mitigation strategies. The use of iPSC-CMs has emerged as a crucial platform for studying chemotherapy-induced cardiotoxicity.
Review
Cell Biology
Xue Jiang, Yihuan Chen, Xiaofeng Liu, Lingqun Ye, Miao Yu, Zhenya Shen, Wei Lei, Shijun Hu
Summary: Researchers have discovered the contribution of genetic defects to the pathogenesis of primary cardiomyopathy and tried to explain the pathogenesis of these diseases by establishing various disease models. The advent of human induced pluripotent stem cells (hiPSCs) provides an unprecedented opportunity to further investigate the pathogenic mechanisms of inherited cardiomyopathies in vitro using patient-specific hiPSC-derived cardiomyocytes. The development of defects in genetically modified animal models differs notably from human diseases at the molecular level.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Chrishan J. A. Ramachandra, Jasper Chua, Shuo Cong, Myu Mai Ja Kp, Winston Shim, Joseph C. Wu, Derek J. Hausenloy
Summary: Normal cardiac functions depend on continuous energy supply. Metabolic disturbances and impaired mitochondrial bioenergetics underlie various cardiac diseases, but specific treatments are lacking. Patient-derived iPSCs show promise for studying cardiomyopathies and novel therapies.
CARDIOVASCULAR RESEARCH
(2021)
Review
Cell & Tissue Engineering
Jiangtao Li, Xin Feng, Xiang Wei
Summary: This review summarizes the methods of establishing cardiomyocyte models using induced pluripotent stem cells (iPSCs) and the progress in genome editing techniques. Because the currently cultured iPSC-CMs are immature, researchers have attempted various methods to promote their maturation. Many researchers have established iPSC-CM models of hypertrophic cardiomyopathy (HCM) and used diverse methods for measurements.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Pharmacology & Pharmacy
Ayesha Arefin, Melissa Mendoza, Keri Dame, M. Iveth Garcia, David G. Strauss, Alexandre J. S. Ribeiro
Summary: We investigated the properties of engineered heart tissues (EHTs) made with different tissue casting batches and lines of differentiated hPSC-cardiomyocytes. The contractile outputs of EHTs were measured using a video-optical assay and compared with monolayers of hPSC-cardiomyocytes cultured in two-dimensional cultures. The drug-induced contractile responses were similar between monolayers and EHTs, and showed a close relationship with calcium kinetics.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cell Biology
Mario G. Pavez-Giani, Lukas Cyganek
Summary: This review summarizes recent advances in iPSC-based disease modeling of mitochondrial cardiomyopathies and explores the patho-mechanistic insights as well as new therapeutic approaches. Researchers have used iPSC technology to recapitulate major characteristics of mitochondrial cardiomyopathies, providing a powerful platform for drug development and testing of new therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Ying Zhang, Jun Wei, Jiani Cao, Kehua Zhang, Yaojin Peng, Hongkui Deng, Jiuhong Kang, Guangjin Pan, Yong Zhang, Boqiang Fu, Shijun Hu, Jie Na, Yan Liu, Lei Wang, Lingmin Liang, Huanxin Zhu, Yu Zhang, Zi-Bing Jin, Jie Hao, Aijin Ma, Tongbiao Zhao, Junying Yu
Summary: "Requirements for Human-Induced Pluripotent Stem Cells" is the first set of guidelines in China on human-induced pluripotent stem cells. It provides detailed technical requirements and aims to promote international standardization.
CELL PROLIFERATION
(2022)
Review
Cell & Tissue Engineering
Kozue Murata, Hidetoshi Masumoto
Summary: The use of human pluripotent stem cells (hPSCs) to create a 3-dimensional structure mimicking human cardiac tissue functions allows for drug discovery and cardiotoxicity testing, with the potential of heart-on-a-chip systems in medical research.
Article
Biochemical Research Methods
Julia Vallverdu, Raquel A. Martinez Garcia de la Torre, Inge Mannaerts, Stefaan Verhulst, Ayla Smout, Mar Coll, Silvia Arino, Teresa Rubio-Tomas, Beatriz Aguilar-Bravo, Celia Martinez-Sanchez, Delia Blaya, Catherine M. Verfaillie, Leo A. van Grunsven, Pau Sancho-Bru
Summary: Human iPSCs are differentiated into HSCs with growth factors for in vitro modeling. The protocol yields iPSC-HSCs with phenotypic and functional characteristics of primary HSCs, suitable for high-throughput in vitro studies. Coculturing iPSC-HSCs with hepatocytes allows for the formation of 3D hepatic spheroids, enabling modeling and drug screening studies.
Article
Pharmacology & Pharmacy
Michelle Vanessa Kamga Kapchoup, Juergen Hescheler, Filomain Nguemo
Summary: Hydroxychloroquine (HDQ) has been widely studied for its potential use in the treatment and prevention of COVID-19. This antimalarial drug has shown beneficial effects on stem cell proliferation and cardiomyocyte activity, but it can also be toxic at high concentrations. Identifying risk factors and understanding the cardiotoxic profile of HDQ is challenging.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Medicine, Research & Experimental
Chunping Liu, Huiqi Chen, Sien Guo, Qiaojing Liu, Zhijun Chen, Haiding Huang, Qi Zhao, Longmei Li, Huan Cen, Zebo Jiang, Qiyuan Luo, Xiaoling Chen, Jiaxiong Zhao, Wensheng Chen, Phillip C. Yang, Lei Wang
Summary: With the progress of tumor treatment, the 5-year survival rate of breast cancer is close to 90%. Cardiovascular toxicity caused by chemotherapy has become a vital factor affecting the survival of patients with breast cancer. This article reviews the toxicity and mechanisms of current clinical anti-breast cancer drugs and proposes strategies for preventing cardiovascular toxicity.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Cardiac & Cardiovascular Systems
Maxwell Kwok, Carrie Lee, Hung Sing Li, Ruixia Deng, Chantelle Tsoi, Qianqian Ding, Suk Ying Tsang, Kam Tong Leung, Bryan P. Yan, Ellen N. Poon
Summary: The study demonstrated that remdesivir can induce cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes at clinically relevant concentrations, including causing mitochondrial damage, reducing redox potential, suppressing mitochondrial respiration, and inducing non-mitochondrial damage, with some of these effects persisting after treatment cessation and leading to cell death.
CARDIOVASCULAR RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Parvin Forghani, Aysha Rashid, Fangxu Sun, Rui Liu, Dong Li, Megan R. Lee, Hyun Hwang, Joshua T. Maxwell, Anant Mandawat, Ronghu Wu, Khalid Salaita, Chunhui Xu
Summary: Anti-cancer therapies have improved patient outcomes, but cardiac side effects from these treatments are still a significant challenge. This study investigated the mechanisms underlying cardiotoxicity induced by the proteasome inhibitor carfilzomib using hiPSC-CMs. The findings showed that carfilzomib treatment caused deleterious changes in cellular and functional characteristics of hiPSC-CMs, affecting mitochondrial function and contractility. Insights into these changes were gained from omic analyses of gene and protein expression.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Cell Biology
Taiki Satoh, Marcelo A. S. Toledo, Janik Boehnke, Kathrin Olschok, Niclas Flosdorf, Katrin Goetz, Caroline Kuestermann, Stephanie Sontag, Kristin Sere, Steffen Koschmieder, Tim H. Bruemmendorf, Nicolas Chatain, Yoh-ichi Tagawa, Martin Zenke
Summary: Dendritic cells (DC) are professional antigen-presenting cells that can be divided into different subsets, with the DC3 subset having proinflammatory properties. Human iPS cell-derived DC3 exhibit similar characteristics to blood DC3 in vitro. The JAK2 V617F mutation enhances DC3 production and biases towards erythrocytes and megakaryocytes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Tarek Magdy, Adam J. T. Schuldt, Joseph C. Wu, Daniel Bernstein, Paul W. Burridge
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 58
(2018)
Editorial Material
Pharmacology & Pharmacy
Tarek Magdy, Paul W. Burridge
Article
Pharmacology & Pharmacy
U. M. Zanger, K. Klein, M. Thomas, J. K. Rieger, R. Tremmel, B. A. Kandel, M. Klein, T. Magdy
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2014)
Editorial Material
Cell & Tissue Engineering
Tarek Magdy, Paul W. Burridge
Review
Cardiac & Cardiovascular Systems
Emily A. Pinheiro, Tarek Magdy, Paul W. Burridge
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2020)
Article
Cell & Tissue Engineering
Hui-Hsuan Kuo, Xiaozhi Gao, Jean-Marc DeKeyser, K. Ashley Fetterman, Emily A. Pinheiro, Carly J. Weddle, Hananeh Fonoudi, Michael V. Orman, Marisol Romero-Tejeda, Mariam Jouni, Malorie Blancard, Tarek Magdy, Conrad L. Epting, Alfred L. George, Paul W. Burridge
Article
Oncology
Purnima Singh, Xuexia Wang, Lindsey Hageman, Yanjun Chen, Tarek Magdy, Wendy Landier, Jill P. Ginsberg, Joseph P. Neglia, Charles A. Sklar, Sharon M. Castellino, Zoann E. Dreyer, Melissa M. Hudson, Leslie L. Robison, Javier G. Blanco, Mary Relling, Paul Burridge, Smita Bhatia
Review
Pharmacology & Pharmacy
Tarek Magdy, Paul W. Burridge
Summary: Anthra-cycline anticancer drugs are known for their potential heart toxicity, and researchers have identified over 60 loci associated with anthracycline-induced cardiotoxicity through pharmacogenomic studies, yet none have been developed into FDA-approved biomarkers. Advances in human-induced pluripotent stem cell-derived cardiomyocytes now allow for validation of variants associated with AIC in a human model.
Article
Multidisciplinary Sciences
Kevin M. Huang, Megan Zavorka Thomas, Tarek Magdy, Eric D. Eisenmann, Muhammad Erfan Uddin, Duncan F. DiGiacomo, Alexander Pan, Markus Keiser, Marcus Otter, Sherry H. Xia, Yang Li, Yan Jin, Qiang Fu, Alice A. Gibson, Ingrid M. Bonilla, Cynthia A. Carnes, Kara N. Corps, Vincenzo Coppola, Sakima A. Smith, Daniel Addison, Anne T. Nies, Ralf Bundschuh, Taosheng Chen, Maryam B. Lustberg, Joanne Wang, Stefan Oswald, Moray J. Campbell, Pearlly S. Yan, Sharyn D. Baker, Shuiying Hu, Paul W. Burridge, Alex Sparreboom
Summary: By studying the critical transporter OCT3 for doxorubicin accumulation in the heart, researchers have revealed the mechanism of doxorubicin-induced cardiotoxicity, providing a theoretical basis for a targeted intervention strategy to prevent this side effect.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell & Tissue Engineering
Tarek Magdy, Zhengxin Jiang, Mariam Jouni, Hananeh Fonoudi, Davi Lyra-Leite, Gwanghyun Jung, Marisol Romero-Tejeda, Hui-Hsuan Kuo, K. Ashley Fetterman, Mennat Gharib, Brian T. Burmeister, Mingming Zhao, Yadav Sapkota, Colin J. Ross, Bruce C. Carleton, Daniel Bernstein, Paul W. Burridge
Summary: A recent study identified a genetic variant associated with anthracycline-induced cardiotoxicity and elucidated its mechanism using hiPSC-CMs. The study found that an RARG agonist can attenuate DIC, providing a new approach for clinical prechemotherapy genetic screening and treatment.
Article
Cardiac & Cardiovascular Systems
Tarek Magdy, Mariam Jouni, Hui-Hsuan Kuo, Carly J. Weddle, Davi Lyra-Leite, Hananeh Fonoudi, Marisol Romero-Tejeda, Mennat Gharib, Hoor Javed, Giovanni Fajardo, Colin J. D. Ross, Bruce C. Carleton, Daniel Bernstein, Paul W. Burridge
Summary: This study demonstrates the cardioprotective effect of the SLC28A3 locus using human induced pluripotent stem cell model. It also identifies a novel cardioprotective single nucleotide polymorphism and a competitive inhibitor, desipramine, against doxorubicin-induced cardiotoxicity.
Editorial Material
Pharmacology & Pharmacy
Tarek Magdy, Paul W. Burridge
Article
Cardiac & Cardiovascular Systems
Purnima Singh, Disheet A. Shah, Mariam Jouni, Romina B. Cejas, David K. Crossman, Tarek Magdy, Shaowei Qiu, Xuexia Wang, Liting Zhou, Noha Sharafeldin, Lindsey Hageman, Donald E. McKenna, Saro H. Armenian, Frank M. Balis, Douglas S. Hawkins, Frank G. Keller, Melissa M. Hudson, Joseph P. Neglia, A. Kim Ritchey, Jill P. Ginsberg, Wendy Landier, Ravi Bhatia, Paul W. Burridge, Smita Bhatia
Summary: This study examined the differential blood-based mRNA expression profiles in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. The results revealed dysregulation of several genes, including LDHA, CD36, IL1R1, IL1R2, MMP8, and MMP9, that are associated with metabolic perturbations, structural remodeling, and symptomatic cardiotoxicity in these survivors.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Multidisciplinary Sciences
Tarek Magdy, Hui-Hsuan Kuo, Paul W. Burridge