Article
Pharmacology & Pharmacy
C. Altrocchi, K. Van Ammel, M. Steemans, M. Kreir, F. Tekle, A. Teisman, D. J. Gallacher, H. R. Lu
Summary: This study developed an in vitro screening platform using human-induced pluripotent stem cell-derived cardiomyocytes to evaluate both acute and delayed electrophysiological and cytotoxic effects of reference compounds, which can contribute to the early assessment of drug-induced cardiotoxicity.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Akshay Narkar, James M. Willard, Ksenia Blinova
Summary: This review focuses on recent advances in chronic cardiotoxicity assessment using cardiomyocytes differentiated from human induced pluripotent stem cells. The review summarizes studies on chronic cardiotoxicity induced by various drugs, including anticancer agents, antibiotics, anti-HCV drugs, and antidiabetic drugs. The review also highlights the use of hiPSC-CMs in investigating the chronic effects of non-pharmaceutical cardiotoxicants and the development of biomarker assays. The comprehensive investigation of long-term repeated exposure-induced effects on cardiomyocytes can provide mechanistic insights and recapitulate drug and environmental cardiotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Joe Z. Zhang, Nadjet Belbachir, Tiejun Zhang, Yu Liu, Rajani Shrestha, Joseph C. Wu
Summary: The study revealed that recovered hiPSC-CMs from cryopreservation showed upregulation of cell cycle genes and altered response to drugs, indicating an increased propensity for drug-induced cardiac arrhythmic events.
Article
Toxicology
Feng Wei, Lisa Pence, Kellie Woodling, Prathyusha Bagam, Richard Beger, Goncalo Gamboa da Costa, Li Pang
Summary: This study compared the electrophysiological responses of hiPSC-CMs to different compounds in serum and serum-free media and explained the reason behind the differences. The study revealed the impact of hydrophobic compound loss in serum-free preparations on drug bioavailability and risk prediction of arrhythmia.
TOXICOLOGICAL SCIENCES
(2022)
Article
Biochemical Research Methods
Shuyun Bai, Junjie Pei, Kan Chen, Ya Zhao, Henghua Cao, Luyang Tian, Yue Ma, Haiheng Dong
Summary: This study systematically investigated the time window of stable ion currents in high-purity hiPSC-derived ventricular cardiomyocytes (hiPSC-vCMs) and confirmed their ability to accurately predict the proarrhythmic risk of CiPA reference compounds. By electrically pacing hiPSC-vCMs at a physiological beating rate using a MEA, drug-induced prolongation of field potential duration and arrhythmia-like events were observed for high- and intermediate-risk drugs. The results provide a simple and feasible method to assess drug proarrhythmic potentials in hiPSC-CMs at a physiological beating rate.
Article
Pharmacology & Pharmacy
William P. Bozza, Kazuyo Takeda, Wei-Lun Alterovitz, Chao-Kai Chou, Rong-Fong Shen, Baolin Zhang
Summary: Anthracyclines are effective chemotherapy drugs but their clinical use is limited by dose-dependent cardiotoxicity. This study used hiPSC-CMs and impedance measurement to monitor cardiomyocyte responses, comparing four structurally similar anthracycline drugs with different cardiotoxicity profiles. Results showed that differences in cardiotoxicity were linked to cardiomyocyte uptake and activation/inhibition of multiple cellular pathways.
Article
Biochemistry & Molecular Biology
Dieter Van de Sande, Mohammadreza Ghasemi, Taylor Watters, Francis Burton, Ly Pham, Cristina Altrocchi, David J. Gallacher, Huarong Lu, Godfrey Smith
Summary: This study found that human induced pluripotent stem cell-derived cardiomyocytes treated to enhance structural maturity are superior to mature ventricular cardiomyocytes in detecting drug-induced changes. The electrophysiological and contractility measurements showed similar results in two different experimental settings, but with slight differences in contraction amplitude, which may be explained by differences in cell-to-matrix adhesion. These findings suggest that both types of 2D culture containing structural matured hiPSC-CMs are equally effective in detecting drug-induced electrophysiological effects in functional safety studies.
Article
Cell Biology
Maria Dago, Teresa Crespo-Garcia, Anabel Camara-Checa, Josu Rapun, Marcos Rubio-Alarcon, Maria Marin, Juan Tamargo, Ricardo Caballero, Eva Delpon
Summary: Dapagliflozin (dapa) and empagliflozin (empa) are drugs that can increase sodium and potassium ion currents in cardiomyocytes, making them a potential new class of antiarrhythmic drugs.
Article
Biochemistry & Molecular Biology
Anne Kayser, Sven Dittmann, Tomo Saric, Giulia Mearini, Arie O. Verkerk, Eric Schulze-Bahr
Summary: This study investigates the pathogenic mechanism of the W101C KCNJ5 mutation in sinus bradycardia, a type of sinus node dysfunction. By generating patient-derived induced pluripotent stem cells (hiPSCs) and correcting the mutation, the researchers were able to differentiate these cells into cardiomyocytes and study their characteristics. The study found that the mutated cardiomyocytes had a constitutively active potassium current and exhibited a slower pacing frequency, indicating the presence of bradycardia. Interestingly, the blockade of the mutated GIRK channel rescued the phenotype. These findings provide insights into the mechanisms underlying sinus node dysfunction and suggest potential treatment options for patients with GIRK channel dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Miyu Okamoto, Kenta Shimba, Akihiro Kamono, Kiyoshi Kotani, Yasuhiko Jimbo
Summary: The study successfully developed a culture system to measure the spatial dynamics of reentry-like activity, revealing that a simple purification process is sufficient to induce reentry-like activity, which occurs mainly through changes in inter-beat intervals and conduction block for initiation and termination.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Toxicology
Shota Yanagida, Ayano Satsuka, Sayo Hayashi, Atsushi Ono, Yasunari Kanda
Summary: This study focused on assessing the cardiotoxicity risk of COVID-19 treatments using hiPSC-CMs, finding that hydroxychloroquine poses a proarrhythmic risk while other drugs have low risks. Therefore, hiPSC-CMs may be a useful tool for evaluating the comprehensive cardiotoxicity caused by COVID-19 treatments in nonclinical settings.
TOXICOLOGICAL SCIENCES
(2021)
Article
Neurosciences
Rebecca A. A. Frederick, Ellen Shih, Vernon L. L. Towle, Alexandra Joshi-Imre, Philip R. R. Troyk, Stuart F. F. Cogan
Summary: This study evaluated the stability of implantable devices and stimulation electrodes in saline and canine visual cortex. The results showed that the AIROF electrodes remained stable during pulsing and maintained consistent performance in vivo.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biophysics
Pooja P. Kanade, Nomin-Erdene Oyunbaatar, Arunkumar Shanmugasundaram, Yun-Jin Jeong, Eung-Sam Kim, Bong-Kee Lee, Dong-Weon Lee
Summary: This study introduces a drug screening platform based on a microelectrode array integrated SU-8 cantilever, which enables simultaneous measurement of electrophysiology and contractility of cardiomyocytes. The feasibility of this platform is verified through drug tests, and it is found that some drugs have greater toxicity to contractility, highlighting the need for a reliable dual measurement platform for assessing cardiotoxicity.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Biotechnology & Applied Microbiology
Zhengjie Liu, Dongxin Xu, Jiaru Fang, Qijian Xia, Wenxi Zhong, Hongbo Li, Zhanyun Huang, Nan Cao, Xingxing Liu, Hui-Jiuan Chen, Ning Hu
Summary: This study developed an integrated electrical signal recording and electrical pulse regulating system based on NPMEA, which can achieve high-throughput detection of intracellular electrical signals and provide a reliable recording tool for cell electro-physiological investigation.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Cell & Tissue Engineering
Yukihiro Saito, Kazufumi Nakamura, Masashi Yoshida, Hiroki Sugiyama, Satoshi Akagi, Toru Miyoshi, Hiroshi Morita, Hiroshi Ito
Summary: This study aimed to determine whether HCN4 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can strengthen the pacing function of the cells. The results showed that HCN4-overexpressing iPSC-CMs exhibited higher spontaneous contraction rates and pacing abilities than non-overexpressing iPSC-CMs. These findings suggest that HCN4 overexpression enhances the pacemaker function of iPSC-CMs, indicating the potential use of this transgenic cell line as a cardiac pacemaker.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Food Science & Technology
Matthew C. White, Li Pang, Xi Yang
FOOD AND CHEMICAL TOXICOLOGY
(2016)
Article
Toxicology
Jianhua Huo, Archana Kamalakar, Xi Yang, Beverly Word, Norman Stockbridge, Beverly Lyn-Cook, Li Pang
TOXICOLOGICAL SCIENCES
(2017)
Article
Toxicology
Ksenia Blinova, Jayna Stohlman, Jose Vicente, Dulciana Chan, Lars Johannesen, Maria P. Hortigon-Vinagre, Victor Zamora, Godfrey Smith, William J. Crumb, Li Pang, Beverly Lyn-Cook, James Ross, Mathew Brock, Stacie Chvatal, Daniel Millard, Loriano Galeotti, Norman Stockbridge, David G. Strauss
TOXICOLOGICAL SCIENCES
(2017)
Article
Multidisciplinary Sciences
Igor B. Gubrij, Amanda K. Pangle, Li Pang, Larry G. Johnson
Article
Toxicology
Jianhua Huo, Feng Wei, Chengzhong Cai, Beverly Lyn-Cook, Li Pang
TOXICOLOGICAL SCIENCES
(2019)
Article
Gastroenterology & Hepatology
Li Pang, Beverly Word, Joshua Xu, Honggang Wang, George Hammons, Shiew-Mei Huang, Beverly Lyn-Cook
GASTROENTEROLOGY RESEARCH AND PRACTICE
(2014)
Article
Cell Biology
Ksenia Blinova, Qianyu Dang, Daniel Millard, Godfrey Smith, Jennifer Pierson, Liang Guo, Mathew Brock, Hua Rong Lu, Udo Kraushaar, Haoyu Zeng, Hong Shi, Xiaoyu Zhang, Kohei Sawada, Tomoharu Osada, Yasunari Kanda, Yuko Sekino, Li Pang, Tromondae K. Feaster, Ralf Kettenhofen, Norman Stockbridge, David G. Strauss, Gary Gintant
Article
Cardiac & Cardiovascular Systems
Li Pang, Philip Sager, Xi Yang, Hong Shi, Frederick Sannajust, Mathew Brock, Joseph C. Wu, Najah Abi-Gerges, Beverly Lyn-Cook, Brian R. Berridge, Norman Stockbridge
CIRCULATION RESEARCH
(2019)
Review
Toxicology
Amy Inselman, Fang Liu, Cheng Wang, Qiang Shi, Li Pang, William Mattes, Matthew White, Beverly Lyn-Cook, Hector Rosas-Hernandez, Elvis Cuevas, Susan Lantz, Syed Imam, Syed Ali, Dayton M. Petibone, Jennifer M. Shemansky, Rui Xiong, Yiying Wang, Priya Tripathi, Xuefei Cao, Robert H. Heflich, William Slikker
TOXICOLOGY IN VITRO
(2020)
Review
Toxicology
Li Pang, Zhichao Liu, Feng Wei, Chengzhong Cai, Xi Yang
Summary: Early detection strategies and improvements in cancer treatment have significantly reduced cancer mortality rates in the US. However, cardiovascular side effects of cancer therapy are common among cancer survivors, making cardiovascular disease the second leading cause of morbidity and mortality in this population. Circulating biomarkers are ideal for detecting and monitoring these side effects. Novel tools such as genetic testing and Omics technologies can help elucidate underlying molecular mechanisms and improve prediction and management of cancer therapy-related cardiotoxicity.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Toxicology
Feng Wei, Lisa Pence, Kellie Woodling, Prathyusha Bagam, Richard Beger, Goncalo Gamboa da Costa, Li Pang
Summary: This study compared the electrophysiological responses of hiPSC-CMs to different compounds in serum and serum-free media and explained the reason behind the differences. The study revealed the impact of hydrophobic compound loss in serum-free preparations on drug bioavailability and risk prediction of arrhythmia.
TOXICOLOGICAL SCIENCES
(2022)
Review
Toxicology
Xi Yang, Alexandre J. S. Ribeiro, Li Pang, David G. Strauss
Summary: Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used in regulatory applications to assess drug-induced cardiotoxicity. However, the predictive capacity of hiPSC-CMs for human cardiac safety in clinical trials is still limited.
TOXICOLOGICAL SCIENCES
(2022)
Article
Toxicology
Li Pang
CURRENT OPINION IN TOXICOLOGY
(2020)
Review
Medicine, Legal
Gary Gintant, Emily Pfeiffer Kaushik, Tromondae Feaster, Sonja Stoelzle-Feix, Yasunari Kanda, Tomoharu Osada, Godfrey Smith, Katherine Czysz, Ralf Kettenhofen, Hua Rong Lu, Beibei Cai, Hong Shi, Todd Joseph Herron, Qianyu Dang, Francis Burton, Li Pang, Martin Traebert, Yama Abassi, Jennifer Beck Pierson, Ksenia Blinova
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2020)