Article
Multidisciplinary Sciences
Vito Vurro, Beatrice Federici, Carlotta Ronchi, Chiara Florindi, Valentina Sesti, Silvia Crasto, Claudia Maniezzi, Camilla Galli, Maria Rosa Antognazza, Chiara Bertarelli, Elisa Di Pasquale, Guglielmo Lanzani, Francesco Lodola
Summary: Non-genetic photostimulation is a growing multidisciplinary field that aims to induce light-sensitivity in living systems using exogeneous phototransducers. In this study, an intramembrane photoswitch (Ziapin2) was proposed for optical pacing of hiPSC-CMs. The effects of light-mediated stimulation on cell properties were investigated, including changes in membrane capacitance, membrane potential (V-m), intracellular Ca2+ dynamics, and cell contractility. The results demonstrate that Ziapin2 can modulate electrical activity and contractility in hiPSC-CMs, offering potential for future cardiac physiology development.
Article
Biochemistry & Molecular Biology
Chih-Hsien Wu, Hsuan-Hwai Lin, Yi-Ying Wu, Yi-Lin Chiu, Li-Yen Huang, Cheng-Chung Cheng, Chung-Chi Yang, Tsung-Neng Tsai
Summary: Coronary artery disease is a major global issue. Patients with coronary artery disease often develop peptic ulcers when receiving aspirin treatment, making panendoscopy with biopsy necessary for diagnosis and treatment. A protocol for generating iPSCs from gastric fibroblasts via biopsy was established, with successful differentiation into functional cardiomyocytes demonstrated. This study represents the first in vitro generation of iPSCs from gastric fibroblasts.
Article
Biotechnology & Applied Microbiology
Diego Balboa, Tom Barsby, Vaino Lithovius, Jonna Saarimaki-Vire, Muhmmad Omar-Hmeadi, Oleg Dyachok, Hossam Montaser, Per-Eric Lund, Mingyu Yang, Hazem Ibrahim, Anna Naatanen, Vikash Chandra, Helena Vihinen, Eija Jokitalo, Jouni Kvist, Jarkko Ustinov, Anni I. Nieminen, Emilia Kuuluvainen, Ville Hietakangas, Pekka Katajisto, Joey Lau, Per-Ola Carlsson, Sebastian Barg, Anders Tengholm, Timo Otonkoski
Summary: Transplanting pancreatic islet cells derived from human pluripotent stem cells has great potential for treating diabetes. This study generated functionally mature stem-cell-derived islets (SC-islets) using an optimized protocol and compared them comprehensively to primary adult islets. The results showed that SC-islets exhibited similar functional properties to adult islets in terms of insulin secretion, electrophysiology, signaling, and exocytosis. Additionally, single-cell transcriptomics revealed a continuous maturation trajectory of SC-islets in vitro and during engraftment in mice, closely resembling that of primary islets.
NATURE BIOTECHNOLOGY
(2022)
Review
Cell & Tissue Engineering
Sofija Vuckovic, Rafeeh Dinani, Edgar E. Nollet, Diederik W. D. Kuster, Jan Willem Buikema, Riekelt H. Houtkooper, Miranda Nabben, Jolanda van der Velden, Birgit Goversen
Summary: Maturation strategies improve the metabolic characteristics of iPSC-CMs, but not to the level of the adult heart. Due to early onset hypertrophy, HCM iPSC-CMs may be less suitable to detect early disease modifiers in HCM and might prove more useful to examine the effects of gene editing and new drugs in advanced disease stages.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Immunology
Hui Yu, Lei Qin, Yunzhi Peng, Wenhui Bai, Zhanli Wang
Summary: The study revealed that exosomes released from hypertrophic cardiomyocytes induced inflammatory responses in macrophages through miR-155, activating various signaling pathways, which may play a crucial role in the development of cardiac hypertrophy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Youchen Yan, Tianxin Long, Qiao Su, Yi Wang, Ken Chen, Tiqun Yang, Guangyin Zhao, Qing Ma, Xiaoyun Hu, Chen Liu, Xinxue Liao, Wang Min, Shujuan Li, Dihua Zhang, Yuedong Yang, William T. Pu, Yugang Dong, Da-Zhi Wang, Yili Chen, Zhan-Peng Huang
Summary: Heart failure is a devastating condition affecting more than 100 million people globally. Previous research has identified the gene CIP as a regulator of cardiac homeostasis under pathological stimulation. This study demonstrates that the cardiac transcription factor GATA4 binds to the promoter of the CIP gene and regulates its expression. The decreased expression of CIP in diseased human hearts and the protective effect of cardiac-specific overexpression of CIP in a mouse model suggest that CIP plays a key role in the transition from cardiac hypertrophy to heart failure. The inhibitory function of CIP on pathologic cardiac remodeling is mediated by the IGF, mTORC2, and TGF-beta signaling pathways.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Kenji Miki, Kohei Deguchi, Misato Nakanishi-Koakutsu, Antonio Lucena-Cacace, Shigeru Kondo, Yuya Fujiwara, Takeshi Hatani, Masako Sasaki, Yuki Naka, Chikako Okubo, Megumi Narita, Ikue Takei, Stephanie C. Napier, Tsukasa Sugo, Sachiko Imaichi, Taku Monjo, Tatsuya Ando, Norihisa Tamura, Kenichi Imahashi, Tomoyuki Nishimoto, Yoshinori Yoshida
Summary: The study reveals that an estrogen-related receptor gamma (ERR gamma) agonist and an S-phase kinase-associated protein 2 inhibitor enhance the maturation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by promoting larger cell size, longer sarcomere length, the presence of transverse tubules, and improved metabolic, contractile, and electrical properties.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Brian X. Wang, Laura Nicastro, Liam Couch, Worrapong Kit-Anan, Barrett Downing, Kenneth T. MacLeod, Cesare M. Terracciano
Summary: Cardiac fibroblast-secreted extracellular vesicles (EVs) play a crucial role in modulating the Ca2+ cycling of cardiomyocytes. These EVs not only alter the function of cardiomyocytes but also enhance the efficiency of Ca2+ handling in induced pluripotent stem cell-derived cardiomyocytes.
Article
Pharmacology & Pharmacy
Sung-Ae Hyun, Chang Youn Lee, Moon Yi Ko, Sun-Hwa Chon, Ye-Ji Kim, Jeong-Wook Seo, Kee K. Kim, Minhan Ka
Summary: Exposure to BPA in human induced pluripotent stem cell-derived cardiomyocytes alters cardiac function, affecting potential, channels, calcium transients, and increasing the risk of arrhythmia.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Eline Simons, Bart Loeys, Maaike Alaerts
Summary: The discovery of induced pluripotent stem cells has allowed the generation of various cell types, including iPSC-derived cardiomyocytes, for different purposes such as disease modelling and drug discovery. While 2D iPSC-CM models have shown promise, they are less mature compared to adult cardiomyocytes. Novel approaches are being developed to create 3D models with added cell types, improving maturity and physiological relevance. This review focuses on the progress in modelling inherited cardiac arrhythmias using both 2D and 3D models, and their application in therapy development and drug testing.
Review
Cell & Tissue Engineering
Jessica C. Garbern, Richard T. Lee
Summary: Current methods to differentiate cardiomyocytes from human pluripotent stem cells inadequately recapitulate complete development, resulting in cardiomyocytes with an immature or fetal-like phenotype. Metabolic changes and mitochondrial dynamics play key roles in the maturation of cardiomyocytes, with the transitions in mitochondria responding to metabolic signals throughout development.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Multidisciplinary Sciences
Karolina Kuenzel, Stephan R. Kuenzel, Kaomei Guan
Summary: The combination of hiPSC and organoid technology allows the generation of 3D human culture systems, providing a means to model human tissue-like structures in vitro. This protocol provides detailed instructions to efficiently generate and characterize self-assembling 3D cardiac organoids using hiPSC-derived cardiomyocytes. Cardiac organoids can serve as 3D-based assay systems with various applications in pharmacological and toxicological research, offering an alternative to animal experiments.
Article
Medicine, Research & Experimental
Grace Huang, Zhongjian Cheng, Alycia Hildebrand, Chunlin Wang, Maria Cimini, Rakija Roy, Anna Maria Lucchese, Cindy Benedict, Vandana Mallaredy, Ajit Magadum, Darukeshwara Joladarashi, Charan Thej, Carolina Gonzalez, May Trungcao, Venkata Naga Srikanth Garikipati, John W. Elrod, Walter J. Koch, Raj Kishore
Summary: This study suggests that diabetes impairs the function of EPC-EVs in repairing ischemic heart damage through changes in histone modification and acetylation. The use of histone deacetylase (HDAC) inhibitors may potentially restore the function of EPC and other stem cells for autologous cell therapy applications.
Review
Cardiac & Cardiovascular Systems
Sophia E. Silver, Ryan W. Barrs, Ying Mei
Summary: Cardiovascular disease is a leading cause of global mortality, and alternative cardiac regenerative therapies, such as hPSC-derived cardiomyocytes, show promising therapeutic potential for heart repair. Despite challenges and limitations, solutions are being explored to address these issues towards successful clinical translation and future perspectives on hPSC-CM transplantation.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Cell Biology
Junaid Afzal, Yamin Liu, Wenqiang Du, Yasir Suhail, Pengyu Zong, Jianlin Feng, Visar Ajeti, Wasim A. Sayyad, Joerg Nikolaus, Maya Yankova, Alix C. Deymier, Lixia Yue, Kshitiz
Summary: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have great potential in clinical models of cardiac pathologies, precision medicine, and drug screening. This study presents a method to accelerate the maturation of hiPSC-CMs on a cardiac mimetic matrix (CMM), resulting in rapid maturation within 30 days and exhibiting adult heart characteristics.
Review
Biology
Esra Cagavi, Arzuhan Koc, Sevilay Sahoglu Goktas
TURKISH JOURNAL OF BIOLOGY
(2016)
Article
Multidisciplinary Sciences
Jonas Schwan, Andrea T. Kwaczala, Thomas J. Ryan, Oscar Bartulos, Yongming Ren, Lorenzo R. Sewanan, Aaron H. Morris, Daniel L. Jacoby, Yibing Qyang, Stuart G. Campbell
SCIENTIFIC REPORTS
(2016)
Article
Cell & Tissue Engineering
Biraja C. Dash, Karen Levi, Jonas Schwan, Jiesi Luo, Oscar Bartulos, Hongwei Wu, Caihong Qiu, Ting Yi, Yongming Ren, Stuart Campbell, Marsha W. Rolle, Yibing Qyang
Article
Cell & Tissue Engineering
Umran Aydemir Sezer, Kevser Ozturk Yavuz, Gizem Ors, Sadik Bay, Basak Aru Aru, Oguz Sogut, Tuba Akgul Caglar, Mehmet Recep Bozkurt, Esra Cagavi Cagavi, Gulderen Yanikkaya Demirel Yanikkaya Demirel, Serdar Sezer, Huseyin Karaca
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2020)
Article
Neurosciences
T. Akgul Caglar, Z. B. Durdu, M. U. Turhan, M. Y. Gunal, M. S. Aydin, G. Ozturk, E. Cagavi
Summary: This study identified sensory neurons innervating the heart tissue using retrograde tracers, with Di-8-ANEPPQ showing the highest labeling efficiency. The bilateral distribution of cardiac afferents in NGs and DRGs was demonstrated through 2D and 3D imaging. The findings provide insights into the spatial distribution and abundance of cardiac sensory neurons.
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
Oncology
Arzuhan Koc, Sevilay Sahoglu Goktas, Tuba Akgul Caglar, Esra Cagavi
Summary: This study provides strategies for replating hiPSC-CMs using different dissociation reagents and extracellular matrix materials, with specific operational recommendations for different stages of cardiac cultures.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Cell Biology
Sevilay Goktas Sahoglu, Yusuf Enes Kazci, Erkan Tuncay, Tugce Torun, Celal Akdeniz, Volkan Tuzcu, Esra Cagavi
Summary: This study investigated the influence of an SCN5A gene variant on tachycardia phenotype by analyzing patient-specific iPSCs and cardiomyocytes. The findings revealed a novel pathogenic SCN5A variant associated with altered Na+ channel kinetics, potentially leading to high excitability and tachycardia phenotype. The patient-derived iPSC-CM model recapitulated clinically relevant characteristics of tachycardia, offering insight into the underlying mechanisms.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Neurosciences
Yusuf Enes Kazci, Sevilay Sahoglu Goktas, Mehmet Serif Aydin, Behnaz Karadogan, Aylin Nebol, Mehmet Ugurcan Turhan, Gurkan Ozturk, Esra Cagavi
Summary: This study provides a comprehensive description of the distribution and morphology of sensory innervation fibers in the murine heart, as well as the structural remodeling of sensory endings in post-MI hearts. These findings improve our understanding of the potential impact of sensory remodeling on autonomic imbalance and cardiac arrhythmia generation.
AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
(2022)
Article
Physiology
Arzuhan Koc, Celal Akdeniz, Esra Cagavi
Summary: The electrophysiological regulation of cardiomyocytes by cardiac macrophages plays a critical role in understanding cardiac disorders and developing new therapies. This study demonstrates the cellular and functional interaction between induced pluripotent stem cell-derived cardiomyocytes and monocyte-derived macrophages in both healthy and arrhythmia disease models. The positive chronotropic effect of macrophages on healthy cardiac cultures and the enhancement of arrhythmic events in mutant macrophages suggest the importance of macrophage function in cardiomyocytes. These findings could contribute to the development of effective immunoregulatory therapies for cardiac arrhythmia.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Neurosciences
Sevilay Goktas Sahoglu, Yusuf Enes Kazci, Behnaz Karadogan, Mehmet Serif Aydin, Aylin Nebol, Mehmet Ugurcan Turhan, Gurkan Ozturk, Esra Cagavi
Summary: The sensory nervous system is crucial for maintaining cardiac function. However, our understanding of cardiac afferents is limited. In this study, we mapped the VGLUT2-expressing cardiac afferent fibers and found that the dorsal side of the heart has higher nerve density compared to the ventral side. We also observed a diverse range of spinal afferent nerve endings that innervate different parts of the heart. In a chronic myocardial infarct model, we observed hyperinnervation at the infarct border zone and denervation at distal sites of the ischemic area. These findings highlight the importance of further studying the functional and physiological consequences of sensory innervation remodeling after ischemic injury.
JOURNAL OF NEUROSCIENCE RESEARCH
(2023)
Meeting Abstract
Immunology
Arzuhan Koc, Celal Akdeniz, Esra Cagavi
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Tuba Akgul Caglar, Mehmet Yalcin Gunal, Mehmet Ugurcan Turhan, Gurkan Ozturk, Esra Cagavi
Summary: Retrograde dyes are commonly used to study neuronal innervations of organs, providing insights into cardiac or neuronal cultures. The experimental data offers practical tips for lowering post-cardiac surgery mortality risks and evaluating staining capacity and fluorescent characteristics of Di-8-ANEPPQ dye. This study also supports the tracing of sensory neurons for various organs.
Article
Engineering, Biomedical
Jiesi Luo, Lingfeng Qin, Mehmet H. Kural, Jonas Schwan, Xia Li, Oscar Bartulos, Xiao-qiang Cong, Yongming Ren, Liqiong Gui, Guangxin Li, Matthew W. Ellis, Peining Li, Darrell N. Kotton, Alan Dardik, Jordan S. Pober, George Tellides, Marsha Rolle, Stuart Campbell, Robert J. Hawley, David H. Sachs, Laura E. Niklason, Yibing Qyang
Article
Medicine, Research & Experimental
Oscar Bartulos, Zhen Wu Zhuang, Yan Huang, Nicole Mikush, Carol Suh, Alda Bregasi, Lin Wang, William Chang, Diane S. Krause, Lawrence H. Young, Jordan S. Pober, Yibing Qyang