دورية أكاديمية
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Advancing Cardiovascular Drug Screening Using Human Pluripotent Stem Cell-Derived Cardiomyocytes.

التفاصيل البيبلوغرافية
العنوان: Advancing Cardiovascular Drug Screening Using Human Pluripotent Stem Cell-Derived Cardiomyocytes.
المؤلفون: Oh J; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI Hub), Daegu 41061, Republic of Korea., Kwon OB; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI Hub), Daegu 41061, Republic of Korea., Park SW; Department of Oral Biochemistry, School of Dentistry, Chonnam National University, Gwangju 61186, Republic of Korea., Kim JW; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI Hub), Daegu 41061, Republic of Korea., Lee H; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI Hub), Daegu 41061, Republic of Korea., Kim YK; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI Hub), Daegu 41061, Republic of Korea., Choi EJ; Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.; Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.; Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea., Jung H; Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.; Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.; Department of Functional Genomics, Korea University of Science and Technology (UST), Daejeon 34113, Republic of Korea., Choi DK; School of Life Science and Biotechnology, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea., Oh BJ; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI Hub), Daegu 41061, Republic of Korea., Min SH; Department of Innovative Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 Jul 21; Vol. 25 (14). Date of Electronic Publication: 2024 Jul 21.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Myocytes, Cardiac*/drug effects , Myocytes, Cardiac*/metabolism , Myocytes, Cardiac*/cytology , Drug Evaluation, Preclinical*/methods , Cell Differentiation*/drug effects , Pluripotent Stem Cells*/drug effects , Pluripotent Stem Cells*/cytology , Pluripotent Stem Cells*/metabolism, Humans ; Cardiovascular Agents/pharmacology ; Calcium/metabolism ; Cardiotoxicity ; High-Throughput Screening Assays/methods ; HEK293 Cells ; Calcium Signaling/drug effects
مستخلص: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have emerged as a promising tool for studying cardiac physiology and drug responses. However, their use is largely limited by an immature phenotype and lack of high-throughput analytical methodology. In this study, we developed a high-throughput testing platform utilizing hPSC-CMs to assess the cardiotoxicity and effectiveness of drugs. Following an optimized differentiation and maturation protocol, hPSC-CMs exhibited mature CM morphology, phenotype, and functionality, making them suitable for drug testing applications. We monitored intracellular calcium dynamics using calcium imaging techniques to measure spontaneous calcium oscillations in hPSC-CMs in the presence or absence of test compounds. For the cardiotoxicity test, hPSC-CMs were treated with various compounds, and calcium flux was measured to evaluate their effects on calcium dynamics. We found that cardiotoxic drugs withdrawn due to adverse drug reactions, including encainide, mibefradil, and cetirizine, exhibited toxicity in hPSC-CMs but not in HEK293-hERG cells. Additionally, in the effectiveness test, hPSC-CMs were exposed to ATX-II, a sodium current inducer for mimicking long QT syndrome type 3, followed by exposure to test compounds. The observed changes in calcium dynamics following drug exposure demonstrated the utility of hPSC-CMs as a versatile model system for assessing both cardiotoxicity and drug efficacy. Overall, our findings highlight the potential of hPSC-CMs in advancing drug discovery and development, which offer a physiologically relevant platform for the preclinical screening of novel therapeutics.
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معلومات مُعتمدة: 2015M3A9C7030181; 2020R1A2C1102300 National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)
فهرسة مساهمة: Keywords: cardiomyocytes; cardiovascular pharmacology; drug screening; high-throughput assays; human pluripotent stem cells
المشرفين على المادة: 0 (Cardiovascular Agents)
SY7Q814VUP (Calcium)
تواريخ الأحداث: Date Created: 20240727 Date Completed: 20240727 Latest Revision: 20240729
رمز التحديث: 20240729
مُعرف محوري في PubMed: PMC11277421
DOI: 10.3390/ijms25147971
PMID: 39063213
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms25147971