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3. Biophysical Stretch Induced Differentiation and Maturation of Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Author

Qin, Jiabin, van Mil, Alain, Sluijter, Joost P. G., Hecker, Markus, Editor-in-Chief, Duncker, Dirk J., Editor-in-Chief, Backs, Johannes, Series Editor, Freichel, Marc, Series Editor, Mayr, Manuel, Series Editor, Pohl, Ulrich, Series Editor, Xiao, Junjie, Series Editor, Merkus, Daphne, Series Editor, and Parker, Sarah, Series Editor

Published
2023
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8. Induced Pluripotent Stem Cells

Author

van Mil, Alain, Neef, Klaus, Balk, Geerthe M., Buikema, Jan Willem, Sluijter, Joost P. G., Doevendans, Pieter A. F. M., Baars, Hubert F., editor, Doevendans, Pieter A. F. M., editor, Houweling, Arjan C., editor, and van Tintelen, J. Peter, editor

Published
2020
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9. Wnt Activation and Reduced Cell-Cell Contact Synergistically Induce Massive Expansion of Functional Human iPSC-Derived Cardiomyocytes

Author

Buikema, Jan W., Lee, Soah, Goodyer, William R., Maas, Renee G., Chirikian, Orlando, Li, Guang, Miao, Yi, Paige, Sharon L., Lee, Daniel, Wu, Haodi, Paik, David T., Rhee, Siyeon, Tian, Lei, Galdos, Francisco X., Puluca, Nazan, Beyersdorf, Benjamin, Hu, James, Beck, Aimee, Venkamatran, Sneha, Swami, Srilatha, Wijnker, Paul, Schuldt, Maike, Dorsch, Larissa M., van Mil, Alain, Red-Horse, Kristy, Wu, Joy Y., Geisen, Caroline, Hesse, Michael, Serpooshan, Vahid, Jovinge, Stefan, Fleischmann, Bernd K., Doevendans, Pieter A., van der Velden, Jolanda, Garcia, K. Christopher, Wu, Joseph C., Sluijter, Joost P.G., and Wu, Sean M.

Published
2020
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11. Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs

Author

Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J., Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A., Serra, Margarida, Voets, Ilja K., Malda, Jos, Castilho, Miguel, van Laake, Linda W., Sluijter, Joost P.G., Sampaio-Pinto, Vasco, van Mil, Alain, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J., Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A., Serra, Margarida, Voets, Ilja K., Malda, Jos, Castilho, Miguel, van Laake, Linda W., Sluijter, Joost P.G., Sampaio-Pinto, Vasco, and van Mil, Alain

Abstract

Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, and transportation, thereby reducing their clinical implementation. In this study, hypothermic preservation (4 °C) and two methods for cryopreservation (i.e., a slow and fast cooling approach to −196 °C and −150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes’ age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.

Published
2024

12. Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs

Author

Experimentele Afd. Cardiologie 2, Regenerative Medicine and Stem Cells, Orthopaedie Onderzoek, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Onderzoek Algemene Cardiologie, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, van Mil, Alain, Experimentele Afd. Cardiologie 2, Regenerative Medicine and Stem Cells, Orthopaedie Onderzoek, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Onderzoek Algemene Cardiologie, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, and van Mil, Alain

Published
2024

13. Vitamin C facilitates direct cardiac reprogramming by inhibiting reactive oxygen species

Author

Experimentele Afd. Cardiologie 2, CDL Nanomedicine, Experimentele Afd. Cardiologie 1, CDL Onderzoek Pasterkamp, Child Health, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Centraal Diagnostisch Laboratorium, Cancer, Regenerative Medicine and Stem Cells, Fang, Juntao, Yang, Qiangbing, Maas, Renée G C, Buono, Michele, Meijlink, Bram, Lotgerink Bruinenberg, Dyonne, Benavente, Ernest Diez, Mokry, Michal, van Mil, Alain, Qian, Li, Goumans, Marie-José, Schiffelers, Raymond, Lei, Zhiyong, Sluijter, Joost P G, Experimentele Afd. Cardiologie 2, CDL Nanomedicine, Experimentele Afd. Cardiologie 1, CDL Onderzoek Pasterkamp, Child Health, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Centraal Diagnostisch Laboratorium, Cancer, Regenerative Medicine and Stem Cells, Fang, Juntao, Yang, Qiangbing, Maas, Renée G C, Buono, Michele, Meijlink, Bram, Lotgerink Bruinenberg, Dyonne, Benavente, Ernest Diez, Mokry, Michal, van Mil, Alain, Qian, Li, Goumans, Marie-José, Schiffelers, Raymond, Lei, Zhiyong, and Sluijter, Joost P G

Published
2024

15. Fusogenic Coiled-Coil Peptides Enhance Lipid Nanoparticle-Mediated mRNA Delivery upon Intramyocardial Administration

Author

Zeng, Ye, primary, Estapé Senti, Mariona, additional, Labonia, M. Clara I., additional, Papadopoulou, Panagiota, additional, Brans, Maike A. D., additional, Dokter, Inge, additional, Fens, Marcel H., additional, van Mil, Alain, additional, Sluijter, Joost P. G., additional, Schiffelers, Raymond M., additional, Vader, Pieter, additional, and Kros, Alexander, additional

Published
2023
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16. Abstract P1093: Safety And Feasibility Of Tissue-engineered Biological Ventricular Assist Devices For Ischemic Cardiomyopathy

Author

Wu, Ming, primary, Van Mil, Alain, additional, Claus, Piet, additional, Algoet, Michiel, additional, Hrynevich, Andrei, additional, Braig, Johannes, additional, Cedillo-Servin, Gerardo, additional, Gillijns, Hilde, additional, Holemans, Patricia, additional, Dokter, Inge, additional, Jüngst, Tomasz, additional, Castilho, Miguel, additional, Malda, Jos, additional, Gröll, Jürgen, additional, Mezo, Manuel, additional, Sluijter, Joost P, additional, Oosterlinck, Wouter, additional, Prosper, Felipe, additional, and Janssens, Stefan P, additional

Published
2023
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18. Convergence of melt electrowriting and extrusion-based bioprinting for vascular patterning of a myocardial construct

Author

Ainsworth, Madison Jade, Chirico, Nino, de Ruijter, Mylène, Hrynevich, Andrei, Dokter, Inge, Sluijter, Joost P G, Malda, Jos, van Mil, Alain, Castilho, Miguel, CS_Locomotion, and Equine Musculoskeletal Biology

Subjects
Engineered heart tissue, Converged biofabrication, Bioprinting, Pre-vascularization, Cardiac tissue engineering, Melt electrowriting, Myocardial tissue engineering
Abstract

To progress cardiac tissue engineering strategies closer to the clinic, thicker constructs are required to meet the functional need following a cardiac event. Consequently, pre-vascularization of these constructs needs to be investigated to ensure survival and optimal performance of implantable engineered heart tissue. The aim of this research is to investigate the potential of combining extrusion-based bioprinting (EBB) and melt electrowriting for the fabrication of a myocardial construct with a precisely patterned pre-vascular pathway. Gelatin methacryloyl (GelMA) was investigated as a base hydrogel for the respective myocardial and vascular bioinks with collagen, Matrigel and fibrinogen as interpenetrating polymers to support myocardial functionality. Subsequently, extrusion-based printability and viability were investigated to determine the optimal processing parameters for printing into melt electrowritten meshes. Finally, an anatomically inspired vascular pathway was implemented in a dual EBB set-up into melt electrowritten meshes, creating a patterned pre-vascularized myocardial construct. It was determined that a blend of 5% GelMA and 0.8 mg·ml -1collagen with a low crosslinked density was optimal for myocardial cellular arrangement and alignment within the constructs. For the vascular fraction, the optimized formulation consisted of 5% GelMA, 0.8 mg·ml -1collagen and 1 mg·ml -1fibrinogen with a higher crosslinked density, which led to enhanced vascular cell connectivity. Printability assessment confirmed that the optimized bioinks could effectively fill the microfiber mesh while supporting cell viability (∼70%). Finally, the two bioinks were applied using a dual EBB system for the fabrication of a pre-vascular pathway with the shape of a left anterior descending artery within a myocardial construct, whereby the distinct cell populations could be visualized in their respective patterns up to D14. This research investigated the first step towards developing a thick engineered cardiac tissue construct in which a pre-vascularization pathway is fabricated within a myocardial construct.

Published
2023

19. Fusogenic Coiled-Coil Peptides Enhance Lipid Nanoparticle-Mediated mRNA Delivery upon Intramyocardial Administration

Author

Zeng, Ye, Estapé Senti, Mariona, Labonia, M. Clara I., Papadopoulou, Panagiota, Brans, Maike A.D., Dokter, Inge, Fens, Marcel H., van Mil, Alain, Sluijter, Joost P.G., Schiffelers, Raymond M., Vader, Pieter, Kros, Alexander, Zeng, Ye, Estapé Senti, Mariona, Labonia, M. Clara I., Papadopoulou, Panagiota, Brans, Maike A.D., Dokter, Inge, Fens, Marcel H., van Mil, Alain, Sluijter, Joost P.G., Schiffelers, Raymond M., Vader, Pieter, and Kros, Alexander

Abstract

Heart failure is a serious condition that results from the extensive loss of specialized cardiac muscle cells called cardiomyocytes (CMs), typically caused by myocardial infarction (MI). Messenger RNA (mRNA) therapeutics are emerging as a very promising gene medicine for regenerative cardiac therapy. To date, lipid nanoparticles (LNPs) represent the most clinically advanced mRNA delivery platform. Yet, their delivery efficiency has been limited by their endosomal entrapment after endocytosis. Previously, we demonstrated that a pair of complementary coiled-coil peptides (CPE4/CPK4) triggered efficient fusion between liposomes and cells, bypassing endosomal entrapment and resulting in efficient drug delivery. Here, we modified mRNA-LNPs with the fusogenic coiled-coil peptides and demonstrated efficient mRNA delivery to difficult-to-transfect induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs). As proof of in vivo applicability of these fusogenic LNPs, local administration via intramyocardial injection led to significantly enhanced mRNA delivery and concomitant protein expression. This represents the successful application of the fusogenic coiled-coil peptides to improve mRNA-LNPs transfection in the heart and provides the potential for the advanced development of effective regenerative therapies for heart failure.

Published
2023

20. Fusogenic Coiled-Coil Peptides Enhance Lipid Nanoparticle-Mediated mRNA Delivery upon Intramyocardial Administration

Author

Afd Pharmaceutics, Pharmaceutics, Zeng, Ye, Estapé Senti, Mariona, Labonia, M. Clara I., Papadopoulou, Panagiota, Brans, Maike A.D., Dokter, Inge, Fens, Marcel H., van Mil, Alain, Sluijter, Joost P.G., Schiffelers, Raymond M., Vader, Pieter, Kros, Alexander, Afd Pharmaceutics, Pharmaceutics, Zeng, Ye, Estapé Senti, Mariona, Labonia, M. Clara I., Papadopoulou, Panagiota, Brans, Maike A.D., Dokter, Inge, Fens, Marcel H., van Mil, Alain, Sluijter, Joost P.G., Schiffelers, Raymond M., Vader, Pieter, and Kros, Alexander

Published
2023

21. Convergence of melt electrowriting and extrusion-based bioprinting for vascular patterning of a myocardial construct

Author

CS_Locomotion, Equine Musculoskeletal Biology, Locomotion - Equine Sciences, Ainsworth, Madison Jade, Chirico, Nino, de Ruijter, Mylène, Hrynevich, Andrei, Dokter, Inge, Sluijter, Joost P G, Malda, Jos, van Mil, Alain, Castilho, Miguel, CS_Locomotion, Equine Musculoskeletal Biology, Locomotion - Equine Sciences, Ainsworth, Madison Jade, Chirico, Nino, de Ruijter, Mylène, Hrynevich, Andrei, Dokter, Inge, Sluijter, Joost P G, Malda, Jos, van Mil, Alain, and Castilho, Miguel

Published
2023

22. Fusogenic Coiled-Coil Peptides Enhance Lipid Nanoparticle-Mediated mRNA Delivery upon Intramyocardial Administration

Author

CDL Nanomedicine, Experimentele Afd. Cardiologie 2, Cardiologie, Orthopaedie Onderzoek, Cancer, Onderzoek Cardiovasculair Reg. Med., Circulatory Health, Regenerative Medicine and Stem Cells, CDL Staf Research, Centraal Diagnostisch Laboratorium, CDL Cluster Onderzoek en Onderwijs, Zeng, Ye, Estapé Senti, Mariona, Labonia, M. Clara I., Papadopoulou, Panagiota, Brans, Maike A.D., Dokter, Inge, Fens, Marcel H., van Mil, Alain, Sluijter, Joost P.G., Schiffelers, Raymond M., Vader, Pieter, Kros, Alexander, CDL Nanomedicine, Experimentele Afd. Cardiologie 2, Cardiologie, Orthopaedie Onderzoek, Cancer, Onderzoek Cardiovasculair Reg. Med., Circulatory Health, Regenerative Medicine and Stem Cells, CDL Staf Research, Centraal Diagnostisch Laboratorium, CDL Cluster Onderzoek en Onderwijs, Zeng, Ye, Estapé Senti, Mariona, Labonia, M. Clara I., Papadopoulou, Panagiota, Brans, Maike A.D., Dokter, Inge, Fens, Marcel H., van Mil, Alain, Sluijter, Joost P.G., Schiffelers, Raymond M., Vader, Pieter, and Kros, Alexander

Published
2023

23. Convergence of melt electrowriting and extrusion-based bioprinting for vascular patterning of a myocardial construct

Author

Orthopaedie Onderzoek, Cardiovasculaire Immunologie, Onderzoek Cardiovasculair Reg. Med., Circulatory Health, Regenerative Medicine and Stem Cells, Experimentele Afd. Cardiologie 2, Other research (not in main researchprogram), Ainsworth, Madison Jade, Chirico, Nino, de Ruijter, Mylène, Hrynevich, Andrei, Dokter, Inge, Sluijter, Joost P.G., Malda, Jos, van Mil, Alain, Castilho, Miguel, Orthopaedie Onderzoek, Cardiovasculaire Immunologie, Onderzoek Cardiovasculair Reg. Med., Circulatory Health, Regenerative Medicine and Stem Cells, Experimentele Afd. Cardiologie 2, Other research (not in main researchprogram), Ainsworth, Madison Jade, Chirico, Nino, de Ruijter, Mylène, Hrynevich, Andrei, Dokter, Inge, Sluijter, Joost P.G., Malda, Jos, van Mil, Alain, and Castilho, Miguel

Published
2023

24. Generation, High-Throughput Screening, and Biobanking of Human-Induced Pluripotent Stem Cell-Derived Cardiac Spheroids

Author

Onderzoek Cardiovasculair Reg. Med., Experimentele Afd. Cardiologie 2, Team Onderzoek, Circulatory Health, Team Medisch, Regenerative Medicine and Stem Cells, Maas, Renee G C, Beekink, Tess, Chirico, Nino, Snijders Blok, Christian J B, Dokter, Inge, Sampaio-Pinto, Vasco, van Mil, Alain, Doevendans, Pieter A, Buikema, Jan W, Sluijter, Joost P G, Stillitano, Francesca, Onderzoek Cardiovasculair Reg. Med., Experimentele Afd. Cardiologie 2, Team Onderzoek, Circulatory Health, Team Medisch, Regenerative Medicine and Stem Cells, Maas, Renee G C, Beekink, Tess, Chirico, Nino, Snijders Blok, Christian J B, Dokter, Inge, Sampaio-Pinto, Vasco, van Mil, Alain, Doevendans, Pieter A, Buikema, Jan W, Sluijter, Joost P G, and Stillitano, Francesca

Published
2023

26. Hypothermic and cryogenic preservation of cardiac tissue-engineered constructsElectronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3bm01908j

Author

Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J., Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A., Serra, Margarida, Voets, Ilja K., Malda, Jos, Castilho, Miguel, van Laake, Linda W., Sluijter, Joost P. G., Sampaio-Pinto, Vasco, and van Mil, Alain

Abstract

Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, and transportation, thereby reducing their clinical implementation. In this study, hypothermic preservation (4 °C) and two methods for cryopreservation (i.e., a slow and fast cooling approach to −196 °C and −150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes’ age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.

Published
2024
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27. Metabolic Maturation Increases Susceptibility to Hypoxia-induced Damage in Human iPSC-derived Cardiomyocytes

Author

Peters, Marijn C, primary, Maas, Renee G C, additional, van Adrichem, Iris, additional, Doevendans, Pieter A M, additional, Mercola, Mark, additional, Šarić, Tomo, additional, Buikema, Jan W, additional, van Mil, Alain, additional, Chamuleau, Steven A J, additional, Sluijter, Joost P G, additional, Hnatiuk, Anna P, additional, and Neef, Klaus, additional

Published
2022
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28. NEXT GENERATION BIOENGINEERED HUMAN MYOCARDIUM

Author

CS_Locomotion, Equine Musculoskeletal Biology, van Mil, Alain, Castilho, Miguel, Chirico, Nino, Ainsworth, Madison J., Dokter, Inge, Maas, Renee G. C., Buikema, Jan Willem, Malda, Jos, Sluijter, Joost P. G., CS_Locomotion, Equine Musculoskeletal Biology, van Mil, Alain, Castilho, Miguel, Chirico, Nino, Ainsworth, Madison J., Dokter, Inge, Maas, Renee G. C., Buikema, Jan Willem, Malda, Jos, and Sluijter, Joost P. G.

Published
2022

29. Metabolic Maturation Increases Susceptibility to Hypoxia-induced Damage in Human iPSC-derived Cardiomyocytes

Author

Peters, Marijn C., Maas, Renee G. C., van Adrichem, Iris, Doevendans, Pieter A. M., Mercola, Mark, Saric, Tomo, Buikema, Jan W., van Mil, Alain, Chamuleau, Steven A. J., Sluijter, Joost P. G., Hnatiuk, Anna P., Neef, Klaus, Peters, Marijn C., Maas, Renee G. C., van Adrichem, Iris, Doevendans, Pieter A. M., Mercola, Mark, Saric, Tomo, Buikema, Jan W., van Mil, Alain, Chamuleau, Steven A. J., Sluijter, Joost P. G., Hnatiuk, Anna P., and Neef, Klaus

Abstract

The development of new cardioprotective approaches using in vivo models of ischemic heart disease remains challenging as differences in cardiac physiology, phenotype, and disease progression between humans and animals influence model validity and prognostic value. Furthermore, economical and ethical considerations have to be taken into account, especially when using large animal models with relevance for conducting preclinical studies. The development of human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has opened new opportunities for in vitro studies on cardioprotective compounds. However, the immature cellular phenotype of iPSC-CMs remains a roadblock for disease modeling. Here, we show that metabolic maturation renders the susceptibility of iPSC-CMs to hypoxia further toward a clinically representative phenotype. iPSC-CMs cultured in a conventional medium did not show significant cell death after exposure to hypoxia. In contrast, metabolically matured (MM) iPSC-CMs showed inhibited mitochondrial respiration after exposure to hypoxia and increased cell death upon increased durations of hypoxia. Furthermore, we confirmed the applicability of MM iPSC-CMs for in vitro studies of hypoxic damage by validating the known cardioprotective effect of necroptosis inhibitor necrostatin-1. Our results provide important steps to improving and developing valid and predictive human in vitro models of ischemic heart disease.

Published
2022

30. Small molecule-mediated rapid maturation of human induced pluripotent stem cell-derived cardiomyocytes

Author

Experimentele Afd. Cardiologie 2, Circulatory Health, Experimentele Afd. Cardiologie 1, Onderzoek Cardiovasculair Reg. Med., Team Onderzoek, Regenerative Medicine and Stem Cells, CDL Nanomedicine, Team Medisch, Chirico, Nino, Kessler, Elise L, Maas, Renée G C, Fang, Juntao, Qin, Jiabin, Dokter, Inge, Daniels, Mark, Šarić, Tomo, Neef, Klaus, Buikema, Jan-Willem, Lei, Zhiyong, Doevendans, Pieter A, Sluijter, Joost P G, van Mil, Alain, Experimentele Afd. Cardiologie 2, Circulatory Health, Experimentele Afd. Cardiologie 1, Onderzoek Cardiovasculair Reg. Med., Team Onderzoek, Regenerative Medicine and Stem Cells, CDL Nanomedicine, Team Medisch, Chirico, Nino, Kessler, Elise L, Maas, Renée G C, Fang, Juntao, Qin, Jiabin, Dokter, Inge, Daniels, Mark, Šarić, Tomo, Neef, Klaus, Buikema, Jan-Willem, Lei, Zhiyong, Doevendans, Pieter A, Sluijter, Joost P G, and van Mil, Alain

Published
2022

31. Metabolic Maturation Increases Susceptibility to Hypoxia-induced Damage in Human iPSC-derived Cardiomyocytes

Author

Cardiologie, Cardiologie onderzoek 2, Onderzoek Cardiovasculair Reg. Med., Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Experimentele Afd. Cardiologie 2, Team Onderzoek, Peters, Marijn C., Maas, Renee G.C., van Adrichem, Iris, Doevendans, Pieter A.M., Mercola, Mark, Šarić, Tomo, Buikema, Jan W., van Mil, Alain, Chamuleau, Steven A.J., Sluijter, Joost P.G., Hnatiuk, Anna P., Neef, Klaus, Cardiologie, Cardiologie onderzoek 2, Onderzoek Cardiovasculair Reg. Med., Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Experimentele Afd. Cardiologie 2, Team Onderzoek, Peters, Marijn C., Maas, Renee G.C., van Adrichem, Iris, Doevendans, Pieter A.M., Mercola, Mark, Šarić, Tomo, Buikema, Jan W., van Mil, Alain, Chamuleau, Steven A.J., Sluijter, Joost P.G., Hnatiuk, Anna P., and Neef, Klaus

Published
2022

32. Follistatin-like 1 promotes proliferation of matured human hypoxic iPSC-cardiomyocytes and is secreted by cardiac fibroblasts

Author

Cardiologie, Cardiologie onderzoek 2, Experimentele Afd. Cardiologie 2, Circulatory Health, Team Medisch, Regenerative Medicine and Stem Cells, Onderzoek Cardiovasculair Reg. Med., Team Onderzoek, Peters, Marijn C., Di Martino, Sofia, Boelens, Thomas, Qin, Jiabin, van Mil, Alain, Doevendans, Pieter A., Chamuleau, Steven A.J., Sluijter, Joost P.G., Neef, Klaus, Cardiologie, Cardiologie onderzoek 2, Experimentele Afd. Cardiologie 2, Circulatory Health, Team Medisch, Regenerative Medicine and Stem Cells, Onderzoek Cardiovasculair Reg. Med., Team Onderzoek, Peters, Marijn C., Di Martino, Sofia, Boelens, Thomas, Qin, Jiabin, van Mil, Alain, Doevendans, Pieter A., Chamuleau, Steven A.J., Sluijter, Joost P.G., and Neef, Klaus

Published
2022

33. Inhibition of miR-25 improves cardiac contractility in the failing heart

Author

Wahlquist, Christine, Jeong, Dongtak, Rojas-Munoz, Agustin, Kho, Changwon, Lee, Ahyoung, Mitsuyama, Shinichi, van Mil, Alain, Park, Woo Jin, Sluijter, Joost P.G., Doevendans, Pieter A.F., Hajjar, Roger J., and Mercola, Mark

Abstract

Heart failure is the culmination of diverse cardiovascular diseases, including hypertension, ischaemic disease and atherosclerosis, valvular insufficiency, myocarditis, and contractile protein mutations, and is uniformly characterized by a progressive loss [...], Heart failure is characterized by a debilitating decline in cardiac function (1), and recent clinical trial results indicate that improving the contractility of heart muscle cells by boosting intracellular calcium handling might be an effective therapy (2,3). MicroRNAs (miRNAs) are dysregulated in heart failure (4,5) but whether they control contractility or constitute therapeutic targets remains speculative. Using high-throughput functional screening of the human microRNAome, here we identify miRNAs that suppress intracellular calcium handling in heart muscle by interacting with messenger RNA encoding the sarcoplasmic reticulum calcium uptake pump SERCA2a (also known as ATP2A2). Of 875 miRNAs tested, miR-25 potently delayed calcium uptake kinetics in cardiomyocytes invitro and was upregulated in heart failure, both in mice and humans. Whereas adeno-associated virus 9 (AAV9)-mediated overexpression of miR-25 in vivo resulted in a significant loss of contractile function, injection of an antisense oligonucleotide (antagomiR) against miR-25 markedly halted established heart failure in a mouse model, improving cardiac function and survival relative to a control antagomiR oligonucleotide. These data reveal that increased expression of endogenous miR-25 contributes to declining cardiac function during heart failure and suggest that it might be targeted therapeutically to restore function.

Published
2014

37. A Roadmap to Cardiac Tissue-Engineered Construct Preservation: Insights from Cells, Tissues, and Organs

Author

Sampaio-Pinto, Vasco, Janssen, Jasmijn, Chirico, Nino, Serra, Margarida, Alves, Paula M., Doevendans, Pieter A., Voets, Ilja K., Sluijter, Joost P.G., van Laake, Linda W., van Mil, Alain, Sampaio-Pinto, Vasco, Janssen, Jasmijn, Chirico, Nino, Serra, Margarida, Alves, Paula M., Doevendans, Pieter A., Voets, Ilja K., Sluijter, Joost P.G., van Laake, Linda W., and van Mil, Alain

Abstract

Worldwide, over 26 million patients suffer from heart failure (HF). One strategy aspiring to prevent or even to reverse HF is based on the transplantation of cardiac tissue-engineered (cTE) constructs. These patient-specific constructs aim to closely resemble the native myocardium and, upon implantation on the diseased tissue, support and restore cardiac function, thereby preventing the development of HF. However, cTE constructs off-the-shelf availability in the clinical arena critically depends on the development of efficient preservation methodologies. Short- and long-term preservation of cTE constructs would enable transportation and direct availability. Herein, currently available methods, from normothermic- to hypothermic- to cryopreservation, for the preservation of cardiomyocytes, whole-heart, and regenerative materials are reviewed. A theoretical foundation and recommendations for future research on developing cTE construct specific preservation methods are provided. Current research suggests that vitrification can be a promising procedure to ensure long-term cryopreservation of cTE constructs, despite the need of high doses of cytotoxic cryoprotective agents. Instead, short-term cTE construct preservation can be achieved at normothermic or hypothermic temperatures by administration of protective additives. With further tuning of these promising methods, it is anticipated that cTE construct therapy can be brought one step closer to the patient.

Published
2021

38. In vitro 3D model and miRNA drug delivery to target calcific aortic valve disease

Author

Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Chemical Engineering, van der Ven, Casper FT, Wu, Pin-Jou, Tibbitt, Mark W, van Mil, Alain, Sluijter, Joost PG, Langer, Robert, Aikawa, Elena, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Chemical Engineering, van der Ven, Casper FT, Wu, Pin-Jou, Tibbitt, Mark W, van Mil, Alain, Sluijter, Joost PG, Langer, Robert, and Aikawa, Elena

Abstract

© 2017 The Author(s). Calcific aortic valve disease (CAVD) is the most prevalent valvular heart disease in the Western population, claiming 17000 deaths per year in the United States and affecting 25% of people older than 65 years of age. Contrary to traditional belief, CAVD is not a passive, degenerative disease but rather a dynamic disease, where initial cellular changes in the valve leaflets progress into fibrotic lesions that induce valve thickening and calcification. Advanced thickening and calcification impair valve function and lead to aortic stenosis (AS). Without intervention, progressive ventricular hypertrophy ensues, which ultimately results in heart failure and death. Currently, aortic valve replacement (AVR), surgical or transcatheter, is the only effective therapy to treat CAVD. However, these costly interventions are often delayed until the late stages of the disease. Nonetheless, 275000 are performed per year worldwide, and this is expected to triple by 2050. Given the current landscape, next-generation therapies for CAVD are needed to improve patient outcome and quality of life. Here, we first provide a background on the aortic valve (AV) and the pathobiology of CAVD as well as highlight current directions and future outlook on the development of functional 3D models of CAVD in vitro. We then consider an often-overlooked aspect contributing to CAVD: miRNA (mis)regulation. Therapeutics could potentially normalize miRNA levels in the early stages of the disease and may slow its progression or even reverse calcification. We close with a discussion of strategies that would enable the use of miRNA as a therapeutic for CAVD. This focuses on an overview of controlled delivery technologies for nucleic acid therapeutics to the valve or other target tissues.

Published
2021

39. Controlled delivery of gold nanoparticle-coupled miRNA therapeutics via an injectable self-healing hydrogel

Author

Circulatory Health, Experimentele Afd. Cardiologie 2, Onderzoek CTC, Regenerative Medicine and Stem Cells, Team Medisch, Onderzoek Cardiovasculair Reg. Med., van der Ven, Casper F T, Tibbitt, Mark W, Conde, João, van Mil, Alain, Hjortnaes, Jesper, Doevendans, Pieter A, Sluijter, Joost P G, Aikawa, Elena, Langer, Robert S, Circulatory Health, Experimentele Afd. Cardiologie 2, Onderzoek CTC, Regenerative Medicine and Stem Cells, Team Medisch, Onderzoek Cardiovasculair Reg. Med., van der Ven, Casper F T, Tibbitt, Mark W, Conde, João, van Mil, Alain, Hjortnaes, Jesper, Doevendans, Pieter A, Sluijter, Joost P G, Aikawa, Elena, and Langer, Robert S

Published
2021

40. miR-132/212 Impairs Cardiomyocytes Contractility in the Failing Heart by Suppressing SERCA2a

Author

Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Arts Assistenten Cardiologie, Experimentele Afd. Cardiologie 2, Genetica, Genetica Sectie Genoomdiagnostiek, Pathologie Laboratorium diagnostiek, Team Medisch, Regenerative Medicine and Stem Cells, Lei, Zhiyong, Wahlquist, Christine, el Azzouzi, Hamid, Deddens, Janine C., Kuster, Diederik, van Mil, Alain, Rojas-Munoz, Agustin, Huibers, Manon M., Mercola, Mark, de Weger, Roel, Van der Velden, Jolanda, Xiao, Junjie, Doevendans, Pieter A., Sluijter, Joost P.G., Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Arts Assistenten Cardiologie, Experimentele Afd. Cardiologie 2, Genetica, Genetica Sectie Genoomdiagnostiek, Pathologie Laboratorium diagnostiek, Team Medisch, Regenerative Medicine and Stem Cells, Lei, Zhiyong, Wahlquist, Christine, el Azzouzi, Hamid, Deddens, Janine C., Kuster, Diederik, van Mil, Alain, Rojas-Munoz, Agustin, Huibers, Manon M., Mercola, Mark, de Weger, Roel, Van der Velden, Jolanda, Xiao, Junjie, Doevendans, Pieter A., and Sluijter, Joost P.G.

Published
2021

41. A Roadmap to Cardiac Tissue-Engineered Construct Preservation: Insights from Cells, Tissues, and Organs

Author

Team Onderzoek, Regenerative Medicine and Stem Cells, Experimentele Afd. Cardiologie 2, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Sampaio-Pinto, Vasco, Janssen, Jasmijn, Chirico, Nino, Serra, Margarida, Alves, Paula M, Doevendans, Pieter A, Voets, Ilja K, Sluijter, Joost P G, van Laake, Linda W, van Mil, Alain, Team Onderzoek, Regenerative Medicine and Stem Cells, Experimentele Afd. Cardiologie 2, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Sampaio-Pinto, Vasco, Janssen, Jasmijn, Chirico, Nino, Serra, Margarida, Alves, Paula M, Doevendans, Pieter A, Voets, Ilja K, Sluijter, Joost P G, van Laake, Linda W, and van Mil, Alain

Published
2021

42. Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23

Author

Onderzoek Precision medicine, Circulatory Health, Child Health, Aios en Stafsecr. Cardiologie, Experimentele Afd. Cardiologie 2, Team Medisch, Onderzoek Cardiovasculair Reg. Med., Garnier, Sophie, Harakalova, Magdalena, Weiss, Stefan, Mokry, Michal, Regitz-Zagrosek, Vera, Hengstenberg, Christian, Cappola, Thomas P, Isnard, Richard, Arbustini, Eloisa, Cook, Stuart A, van Setten, Jessica, Calis, Jorg J A, Hakonarson, Hakon, Morley, Michael P, Stark, Klaus, Prasad, Sanjay K, Li, Jin, O'Regan, Declan P, Grasso, Maurizia, Müller-Nurasyid, Martina, Meitinger, Thomas, Empana, Jean-Philippe, Strauch, Konstantin, Waldenberger, Melanie, Marguiles, Kenneth B, Seidman, Christine E, Kararigas, Georgios, Meder, Benjamin, Haas, Jan, Boutouyrie, Pierre, Lacolley, Patrick, Jouven, Xavier, Erdmann, Jeanette, Blankenberg, Stefan, Wichter, Thomas, Ruppert, Volker, Tavazzi, Luigi, Dubourg, Olivier, Roizes, Gérard, Dorent, Richard, de Groote, Pascal, Fauchier, Laurent, Trochu, Jean-Noël, Aupetit, Jean-François, Bilinska, Zofia T, Germain, Marine, Völker, Uwe, Hemerich, Daiane, Raji, Ibticem, Bacq-Daian, Delphine, Proust, Carole, Remior, Paloma, Gomez-Bueno, Manuel, Lehnert, Kristin, Maas, Renee, Olaso, Robert, Saripella, Ganapathi Varma, Felix, Stephan B, McGinn, Steven, Duboscq-Bidot, Laëtitia, van Mil, Alain, Besse, Céline, Fontaine, Vincent, Blanché, Hélène, Ader, Flavie, Keating, Brendan, Curjol, Angélique, Boland, Anne, Komajda, Michel, Cambien, François, Deleuze, Jean-François, Dörr, Marcus, Asselbergs, Folkert W, Villard, Eric, Trégouët, David-Alexandre, Charron, Philippe, Maas, Renee GC, Onderzoek Precision medicine, Circulatory Health, Child Health, Aios en Stafsecr. Cardiologie, Experimentele Afd. Cardiologie 2, Team Medisch, Onderzoek Cardiovasculair Reg. Med., Garnier, Sophie, Harakalova, Magdalena, Weiss, Stefan, Mokry, Michal, Regitz-Zagrosek, Vera, Hengstenberg, Christian, Cappola, Thomas P, Isnard, Richard, Arbustini, Eloisa, Cook, Stuart A, van Setten, Jessica, Calis, Jorg J A, Hakonarson, Hakon, Morley, Michael P, Stark, Klaus, Prasad, Sanjay K, Li, Jin, O'Regan, Declan P, Grasso, Maurizia, Müller-Nurasyid, Martina, Meitinger, Thomas, Empana, Jean-Philippe, Strauch, Konstantin, Waldenberger, Melanie, Marguiles, Kenneth B, Seidman, Christine E, Kararigas, Georgios, Meder, Benjamin, Haas, Jan, Boutouyrie, Pierre, Lacolley, Patrick, Jouven, Xavier, Erdmann, Jeanette, Blankenberg, Stefan, Wichter, Thomas, Ruppert, Volker, Tavazzi, Luigi, Dubourg, Olivier, Roizes, Gérard, Dorent, Richard, de Groote, Pascal, Fauchier, Laurent, Trochu, Jean-Noël, Aupetit, Jean-François, Bilinska, Zofia T, Germain, Marine, Völker, Uwe, Hemerich, Daiane, Raji, Ibticem, Bacq-Daian, Delphine, Proust, Carole, Remior, Paloma, Gomez-Bueno, Manuel, Lehnert, Kristin, Maas, Renee, Olaso, Robert, Saripella, Ganapathi Varma, Felix, Stephan B, McGinn, Steven, Duboscq-Bidot, Laëtitia, van Mil, Alain, Besse, Céline, Fontaine, Vincent, Blanché, Hélène, Ader, Flavie, Keating, Brendan, Curjol, Angélique, Boland, Anne, Komajda, Michel, Cambien, François, Deleuze, Jean-François, Dörr, Marcus, Asselbergs, Folkert W, Villard, Eric, Trégouët, David-Alexandre, Charron, Philippe, and Maas, Renee GC

Published
2021

43. Cardiac circadian rhythms in time and space: The future is in 4D

Author

Experimentele Afd. Cardiologie 2, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Onderzoek Cardiovasculair Reg. Med., Chirico, Nino, Van Laake, Linda W, Sluijter, Joost P G, van Mil, Alain, Dierickx, Pieterjan, Experimentele Afd. Cardiologie 2, Team Medisch, Circulatory Health, Regenerative Medicine and Stem Cells, Onderzoek Cardiovasculair Reg. Med., Chirico, Nino, Van Laake, Linda W, Sluijter, Joost P G, van Mil, Alain, and Dierickx, Pieterjan

Published
2021

44. miR-132/212 Impairs Cardiomyocytes Contractility in the Failing Heart by Suppressing SERCA2a

Author

Lei, Zhiyong, primary, Wahlquist, Christine, additional, el Azzouzi, Hamid, additional, Deddens, Janine C., additional, Kuster, Diederik, additional, van Mil, Alain, additional, Rojas-Munoz, Agustin, additional, Huibers, Manon M., additional, Mercola, Mark, additional, de Weger, Roel, additional, Van der Velden, Jolanda, additional, Xiao, Junjie, additional, Doevendans, Pieter A., additional, and Sluijter, Joost P. G., additional

Published
2021
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45. Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23

Author

Garnier, Sophie, primary, Harakalova, Magdalena, additional, Weiss, Stefan, additional, Mokry, Michal, additional, Regitz-Zagrosek, Vera, additional, Hengstenberg, Christian, additional, Cappola, Thomas P, additional, Isnard, Richard, additional, Arbustini, Eloisa, additional, Cook, Stuart A, additional, van Setten, Jessica, additional, Calis, Jorg J A, additional, Hakonarson, Hakon, additional, Morley, Michael P, additional, Stark, Klaus, additional, Prasad, Sanjay K, additional, Li, Jin, additional, O'Regan, Declan P, additional, Grasso, Maurizia, additional, Müller-Nurasyid, Martina, additional, Meitinger, Thomas, additional, Empana, Jean-Philippe, additional, Strauch, Konstantin, additional, Waldenberger, Melanie, additional, Marguiles, Kenneth B, additional, Seidman, Christine E, additional, Kararigas, Georgios, additional, Meder, Benjamin, additional, Haas, Jan, additional, Boutouyrie, Pierre, additional, Lacolley, Patrick, additional, Jouven, Xavier, additional, Erdmann, Jeanette, additional, Blankenberg, Stefan, additional, Wichter, Thomas, additional, Ruppert, Volker, additional, Tavazzi, Luigi, additional, Dubourg, Olivier, additional, Roizes, Gérard, additional, Dorent, Richard, additional, de Groote, Pascal, additional, Fauchier, Laurent, additional, Trochu, Jean-Noël, additional, Aupetit, Jean-François, additional, Bilinska, Zofia T, additional, Germain, Marine, additional, Völker, Uwe, additional, Hemerich, Daiane, additional, Raji, Ibticem, additional, Bacq-Daian, Delphine, additional, Proust, Carole, additional, Remior, Paloma, additional, Gomez-Bueno, Manuel, additional, Lehnert, Kristin, additional, Maas, Renee, additional, Olaso, Robert, additional, Saripella, Ganapathi Varma, additional, Felix, Stephan B, additional, McGinn, Steven, additional, Duboscq-Bidot, Laëtitia, additional, van Mil, Alain, additional, Besse, Céline, additional, Fontaine, Vincent, additional, Blanché, Hélène, additional, Ader, Flavie, additional, Keating, Brendan, additional, Curjol, Angélique, additional, Boland, Anne, additional, Komajda, Michel, additional, Cambien, François, additional, Deleuze, Jean-François, additional, Dörr, Marcus, additional, Asselbergs, Folkert W, additional, Villard, Eric, additional, Trégouët, David-Alexandre, additional, and Charron, Philippe, additional

Published
2021
Full Text
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50. Transcriptional regulation profiling reveals disrupted lipid metabolism in failing hearts with a pathogenic phospholamban mutation

Author

Pei, Jiayi, primary, Maas, Renee G.C., additional, Nagyova, Ema, additional, Gho, Johannes M.I.H., additional, Blok, Christian Snijders, additional, van Adrichem, Iris, additional, Calis, Jorg J.A., additional, van Es, René, additional, Sepehrkhouy, Shahrzad, additional, Feyen, Dries, additional, van den Dungen, Noortje, additional, Lansu, Nico, additional, de Jonge, Nicolaas, additional, den Ruijter, Hester M., additional, Huibers, Manon M.H., additional, de Weger, Roel A., additional, van Laake, Linda W., additional, Verhaar, Marianne C., additional, van Tintelen, Peter, additional, van Steenbeek, Frank G., additional, van Mil, Alain, additional, Buikema, Jan W., additional, Burgering, Boudewijn, additional, Kararikes, Ioannis, additional, Mercola, Mark, additional, Doevendans, Pieter A., additional, Sluijter, Joost, additional, Vink, Aryan, additional, Cheng, Caroline, additional, Mokry, Michal, additional, Asselbergs, Folkert W., additional, and Harakalova, Magdalena, additional

Published
2020
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