Article
Cardiac & Cardiovascular Systems
Raquel Nunez-Toldra, Thomas Kirwin, Elisa Ferraro, Fotios G. Pitoulis, Laura Nicastro, Ifigeneia Bardi, Worrapong Kit-Anan, Julia Gorelik, Andre R. Simon, Cesare M. Terracciano
Summary: Altered mechanical load contributes to myocardial interstitial fibrosis. Living myocardial slices respond to varying degrees of mechanical preload by showing changes in cellular, molecular, and functionality related to fibrosis. Modulation of mechano-sensitive mechanisms with TGF-beta R blocker presents potential therapeutic strategies for cardiac fibrosis.
Review
Biotechnology & Applied Microbiology
Hye Sook Shin, Heather Hyeyoon Shin, Yasuhiro Shudo
Summary: Establishing an appropriate disease model, frequent modifications to surgical procedures, and insufficient transparency in reporting are three major inhibitors in current preclinical myocardial infarction research.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Fotios G. Pitoulis, Raquel Nunez-Toldra, Ke Xiao, Worrapong Kit-Anan, Saskia Mitzka, Richard J. Jabbour, Sian E. Harding, Filippo Perbellini, Thomas Thum, Pieter P. de Tombe, Cesare M. Terracciano
Summary: We developed a novel methodology to study chronic load in vitro by using a bioreactor that can recreate the electromechanical events of in vivo pressure-volume loops. Rat living myocardial slices (LMS) were cultured for 3 days with the bioreactor to simulate physiological load, pressure-overload, or volume-overload. The results showed that both pressure- and volume-overloaded LMS exhibited decreased contractility, with volume-overload showing more pronounced effects. Cardiomyocyte hypertrophy and dysregulation of signaling pathways were also observed.
CARDIOVASCULAR RESEARCH
(2022)
Review
Cardiac & Cardiovascular Systems
Elisa Mohr, Thomas Thum, Christian Baer
Summary: In vitro modeling of the heart is a challenging task in cardiovascular research. Three-dimensional cultivation methods have emerged as a solution to overcome the limitations of traditional two-dimensional cultivation. These methods aim to study the fundamental features of the heart and have great potential in disease research, drug screening, and regenerative therapy. However, there is a need for continuous improvement and adaptation to address limitations such as cardiomyocyte maturation and vascularization.
EUROPEAN JOURNAL OF HEART FAILURE
(2022)
Review
Pharmacology & Pharmacy
Iqra Ilyas, Peter J. Little, Zhiping Liu, Yanyong Xu, Danielle Kamato, Bradford C. Berk, Jianping Weng, Suowen Xu
Summary: This article reviews the current use and translational potential of mouse models in atherosclerosis research and drug discovery. Atherosclerotic cardiovascular disease is a chronic and progressive metabolic and inflammatory disease that causes premature human mortality. Despite promising preclinical studies, many drug candidates have not been translated to clinical use due to the complex disease mechanisms involved.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Camille Jubelin, Javier Munoz-Garcia, Laurent Griscom, Denis Cochonneau, Emilie Ollivier, Marie-Francoise Heymann, Francois M. Vallette, Lisa Oliver, Dominique Heymann
Summary: Cancer is a complex disease that requires multidimensional models to understand its development and drug response. Three-dimensional cell culture models, compared to traditional two-dimensional cultures, better mimic the biological behavior of tumor cells and provide a better platform for studying therapeutic escape and drug resistance.
CELL AND BIOSCIENCE
(2022)
Article
Cardiac & Cardiovascular Systems
Jianyi Zhang, Roberto Bolli, Daniel J. Garry, Eduardo Marban, Philippe Menasche, Wolfram-Hubertus Zimmermann, Timothy J. Kamp, Joseph C. Wu, Victor J. Dzau
Summary: This paper provides an update on the recent preclinical and clinical trials using cell therapy and engineered heart tissues for postinfarction left ventricular remodeling and heart failure. The authors discuss novel approaches for cardiac remuscularization through activating proliferative mechanisms or direct reprogramming, aiming to facilitate the translation of discoveries in regenerative myocardial therapies to the clinic.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Flavia Carton, Manuela Malatesta
Summary: Nanoconstructs developed for biomedical purposes need to overcome biological barriers. In vivo models are complex and limited, so simplified in vitro models are preferred. Various in vitro models have been set up, including 2D cell cultures, cell monolayers, 3D cell cultures, and bioreactors. This review provides an overview of the most representative and performing in vitro models for studying biological barriers in nanomedical research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Urology & Nephrology
Neil A. Hukriede, Danielle E. Soranno, Veronika Sander, Tayla Perreau, Michelle C. Starr, Peter S. T. Yuen, Leah J. Siskind, Michael P. Hutchens, Alan J. Davidson, David M. Burmeister, Sarah Faubel, Mark P. de Caestecker
Summary: Models used in preclinical research often have limitations that result in results inconsistent with clinical practice. In the field of acute kidney injury (AKI), clinical trial failures are mainly attributed to inaccurate modeling in rodents. Currently, emerging research methods such as human kidney organoids, zebrafish, rodent, and large animal models are being applied in preclinical therapeutic research. However, the traditional preclinical research methods often overlook the limitations of model systems, leading to misleading results in the preclinical stage of treatment effectiveness. To address this problem, a more flexible and integrated approach is needed, with investigator teams using different model systems closely collaborating with clinical researchers to develop more targeted treatment methods. This review summarizes the current state of acute kidney injury model development and emphasizes the importance of adopting a multidisciplinary approach to optimize the development of treatment methods for acute kidney injury.
NATURE REVIEWS NEPHROLOGY
(2022)
Review
Oncology
Guilherme Ribeiro Romualdo, Kaat Leroy, Cicero Julio Silva Costa, Gabriel Bacil Prata, Bart Vanderborght, Tereza Cristina Da Silva, Luis Fernando Barbisan, Wellington Andraus, Lindsey Devisscher, Niels Olsen Saraiva Camara, Mathieu Vinken, Bruno Cogliati
Summary: Hepatocellular carcinoma (HCC) is a highly incident and deadly malignant neoplasia, with few available anti-HCC drugs. The development of HCC models is essential to understanding the disease and improving diagnostic and therapeutic strategies. Various molecular factors contribute to the pathogenesis of HCC, making the establishment of accurate models crucial for translational research.
Review
Physiology
Jorik H. Amesz, Lu Zhang, Bian R. Everts, Natasja M. S. De Groot, Yannick J. H. J. Taverne
Summary: Living myocardial slices (LMS) offer a comprehensive model for cardiac arrhythmia research. The introduction of biomimetic electromechanical cultivation chambers has facilitated long-term cultivation and control of living myocardial slices culture conditions. This review aims to present the potential of this biomimetic interface in electrophysiological studies,discussing advantages, disadvantages, and future perspectives of the model, as well as various electrophysiological techniques and their application on living myocardial slices.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Immunology
Yinxi Zhou, Jinghua Xia, Shuonan Xu, Tao She, Yanning Zhang, Ying Sun, Miaomiao Wen, Tao Jiang, Yanlu Xiong, Jie Lei
Summary: The development and growth of tumors pose a significant and ongoing threat to human life globally. Despite the remarkable progress achieved by advanced therapeutic strategies such as immune checkpoint therapy and CAR-T in treating solid and hematological malignancies, the malignant initiation and progression of cancer remains controversial and requires further research. Experimental animal models not only have great advantages in simulating tumor occurrence, development, and malignant transformation mechanisms, but also can be used to evaluate the therapeutic effects of diverse clinical interventions, gradually becoming indispensable in cancer research. This paper reviews recent research progress in mouse and rat models, focusing on spontaneous, induced, transgenic, and transplantable tumor models, aiming to provide guidance for future studies on malignant mechanisms and tumor prevention.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Nanoscience & Nanotechnology
Wenkun Dou, Manpreet Malhi, Qili Zhao, Li Wang, Zongjie Huang, Junhui Law, Na Liu, Craig A. Simmons, Jason T. Maynes, Yu Sun
Summary: Heart-on-a-chip platforms show promise for establishing cardiac cell/tissue models in vitro. However, challenges remain in accurately evaluating the contractile functions of these models. Developing new platforms and technologies is essential for understanding cell/tissue physiologies, drug responses, and cardiac diseases. This review discusses recent advances in biosensing platforms and their applications in fundamental research, drug testing, and disease modeling. The challenges and future prospects of heart-on-a-chip platforms for measuring cardiac functional properties are also discussed.
MICROSYSTEMS & NANOENGINEERING
(2022)
Review
Cardiac & Cardiovascular Systems
YingYan Zhu, Dan Jackson, Benjamin Hunter, Lorna Beattie, Lisa Turner, Brett D. Hambly, Richmond W. Jeremy, Cassandra Malecki, Elizabeth N. Robertson, Amy Li, Cris dos Remedios, David Richmond, Christopher Semsarian, John F. O'Sullivan, Paul G. Bannon, Sean Lal
Summary: Biobanking in healthcare has evolved to become essential for modern medical research, with cardiovascular tissue biobanking providing a unique opportunity for translational research into heart failure and related pathologies. However, challenges like data collection, privacy issues, consent, and governance still need to be addressed in order to fully maximize the potential of tissue biobanking for advancing precision medicine in cardiovascular pathology.
Review
Biochemistry & Molecular Biology
Thomas Grewal, Carles Rentero, Carlos Enrich, Mohamed Wahba, Carsten A. Raabe, Ursula Rescher
Summary: Routine manipulation of the mouse genome has become a landmark in biomedical research, allowing for investigation of traits associated with advanced developmental stages. The annexins, a family of calcium- and lipid-binding proteins, have been extensively studied in cellular functions, with recent research on genetically modified annexin mouse models revealing striking phenotypes under stress conditions mimicking human disease. This comprehensive review emphasizes the exciting potential of using animal models in annexin-related research for relevant issues in biology and experimental medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Filippo Perbellini, Thomas Thum
EUROPEAN HEART JOURNAL
(2020)
Article
Cardiac & Cardiovascular Systems
Konstantinos Kalogeras, Richard J. Jabbour, Neil Ruparelia, Samuel Watson, Tito Kabir, Toru Naganuma, Manolis Vavuranakis, Sunao Nakamura, Iqbal S. Malik, Ghada Mikhail, Miles Dalby, Vasileios Panoulas
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
(2020)
Review
Cardiac & Cardiovascular Systems
Naisam Abbas, Filippo Perbellini, Thomas Thum
BASIC RESEARCH IN CARDIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Maximilian Fuchs, Fabian Philipp Kreutzer, Lorenz A. Kapsner, Saskia Mitzka, Annette Just, Filippo Perbellini, Cesare M. Terracciano, Ke Xiao, Robert Geffers, Christian Bogdan, Hans-Ulrich Prokosch, Jan Fiedler, Thomas Thum, Meik Kunz
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Cardiac & Cardiovascular Systems
S. A. Watson, A. Dendorfer, T. Thum, F. Perbellini
BASIC RESEARCH IN CARDIOLOGY
(2020)
Review
Cardiac & Cardiovascular Systems
M. Sansonetti, F. J. G. Waleczek, M. Jung, T. Thum, F. Perbellini
BASIC RESEARCH IN CARDIOLOGY
(2020)
Article
Cardiac & Cardiovascular Systems
Fotios G. Pitoulis, Raquel Nunez-Toldra, Ke Xiao, Worrapong Kit-Anan, Saskia Mitzka, Richard J. Jabbour, Sian E. Harding, Filippo Perbellini, Thomas Thum, Pieter P. de Tombe, Cesare M. Terracciano
Summary: We developed a novel methodology to study chronic load in vitro by using a bioreactor that can recreate the electromechanical events of in vivo pressure-volume loops. Rat living myocardial slices (LMS) were cultured for 3 days with the bioreactor to simulate physiological load, pressure-overload, or volume-overload. The results showed that both pressure- and volume-overloaded LMS exhibited decreased contractility, with volume-overload showing more pronounced effects. Cardiomyocyte hypertrophy and dysregulation of signaling pathways were also observed.
CARDIOVASCULAR RESEARCH
(2022)
Article
Urology & Nephrology
Samuel A. Watson, Kerry-Lee Rosenberg, Kate Bramham, Helen Alston
JOURNAL OF NEPHROLOGY
(2022)
Article
Physiology
Fotios G. Pitoulis, Jacob J. Smith, Blanca Pamias-Lopez, Pieter P. de Tombe, Danika Hayman, Cesare M. Terracciano
Summary: The central question of this study is whether cardiac tissues can be cultured under conditions that do not simulate the mechanical load the heart is exposed to in vivo. The main finding is the development of a culture bioreactor called MyoLoop that can keep living heart tissue alive in vitro under continuous electromechanical stimulation. MyoLoop can simulate the cardiac cycle on a beating slice during culture, recreating the in vivo workload of the heart in vitro. MyoLoop is a novel translational platform for cardiac studies.
EXPERIMENTAL PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
M. A. Zabielska-Kaczorowska, A. E. Bogucka, K. Macur, P. Czaplewska, S. A. Watson, F. Perbellini, C. M. Terracciano, R. T. Smolenski
Summary: In this study, a special in vitro model using ultrathin cardiac slices was used to investigate the proteomic changes in response to electromechanical stimulation. The findings revealed significant alterations related to mitochondrial respiration, energy metabolism, and muscle contraction in stretched slices and fresh myocardial slices cultured without electromechanical stimulation.
SCIENTIFIC REPORTS
(2022)