Three-dimensional co-culturing of stem cell-derived cardiomyocytes and cardiac fibroblasts reveals a role for both cell types in Marfan-related cardiomyopathy
- Author
- Jeffrey Aalders (UGent) , Laurens Léger (UGent) , Louis Van der Meeren (UGent) , Sanjay Sinha, Andre Skirtach (UGent) , Julie De Backer (UGent) and Jolanda van Hengel (UGent)
- Organization
- Project
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- Human stem cell-derived models to unveil mechanisms of impaired myocardial function in Marfan Syndrome
- Atomic force microscopy (AFM) - nanobiotechnology gebaseerd platform voor het bereiken van de dynamiek van afzonderlijke moleculen tot veelzijdige materialen en celmechanica
- Mechanobiology control of immunogenic cell death by bio-polymers for cancer therapy
- It takes two to tango_ a decryption of Marfan cardiomyopathy using human iPSC- derived cardiac cells and engineered heart tissues
- Abstract
- Pathogenic variants in the FBN1 gene, which encodes the extracellular matrix protein fibrillin-1, cause Marfan syndrome (MFS), which affects multiple organ systems, including the cardiovascular system. Myocardial dysfunction has been observed in a subset of patients with MFS and in several MFS mouse models. However, there is limited understanding of the intrinsic consequences of FBN1 variants on cardiomyocytes (CMs). To elucidate the CM-specific contribution in Marfan's cardiomyopathy, cardiosphere cultures of CMs and cardiac fibroblasts (CFs) are used. CMs and CFs were derived by human induced pluripotent stem cell (iPSC) differentiation from MFS iPSCs with a pathogenic variant in FBN1 (c.3725G>A; p.Cys1242Tyr) and the corresponding CRISPR-corrected iPSC line (Cor). Cardiospheres containing MFS CMs show decreased FBN1, COL1A2 and GJA1 expression. MFS CMs cultured in cardiospheres have fewer binucleated CMs in comparison with Cor CMs. 13% of MFS CMs in cardiospheres are binucleated and 15% and 16% in cardiospheres that contain co-cultures with respectively MFS CFs and Cor CFs, compared to Cor CMs, that revealed up to 23% binucleation when co-cultured with CFs. The sarcomere length of CMs, as a marker of development, is significantly increased in MFS CMs interacting with Cor CF or MFS CF, as compared to monocultured MFS CMs. Nuclear blebbing was significantly more frequent in MFS CFs, which correlated with increased stiffness of the nuclear area compared to Cor CFs. Our cardiosphere model for Marfan-related cardiomyopathy identified a contribution of CFs in Marfan-related cardiomyopathy and suggests that abnormal early development of CMs may play a role in the disease mechanism.
- Keywords
- Marfan syndrome, Fibrillin-1, Cardiomyocytes, Cardiac fibroblasts, Disease modelling, Extracellular matrix, NUCLEAR MORPHOLOGY, MATURATION, GENERATION, DIFFERENTIATION, MICROTISSUES, CONNEXIN43, DYNAMICS
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01HQ0AARBWWFJ3HNEGHZPAZH3D
- MLA
- Aalders, Jeffrey, et al. “Three-Dimensional Co-Culturing of Stem Cell-Derived Cardiomyocytes and Cardiac Fibroblasts Reveals a Role for Both Cell Types in Marfan-Related Cardiomyopathy.” MATRIX BIOLOGY, vol. 126, 2024, pp. 14–24, doi:10.1016/j.matbio.2024.01.003.
- APA
- Aalders, J., Léger, L., Van der Meeren, L., Sinha, S., Skirtach, A., De Backer, J., & van Hengel, J. (2024). Three-dimensional co-culturing of stem cell-derived cardiomyocytes and cardiac fibroblasts reveals a role for both cell types in Marfan-related cardiomyopathy. MATRIX BIOLOGY, 126, 14–24. https://doi.org/10.1016/j.matbio.2024.01.003
- Chicago author-date
- Aalders, Jeffrey, Laurens Léger, Louis Van der Meeren, Sanjay Sinha, Andre Skirtach, Julie De Backer, and Jolanda van Hengel. 2024. “Three-Dimensional Co-Culturing of Stem Cell-Derived Cardiomyocytes and Cardiac Fibroblasts Reveals a Role for Both Cell Types in Marfan-Related Cardiomyopathy.” MATRIX BIOLOGY 126: 14–24. https://doi.org/10.1016/j.matbio.2024.01.003.
- Chicago author-date (all authors)
- Aalders, Jeffrey, Laurens Léger, Louis Van der Meeren, Sanjay Sinha, Andre Skirtach, Julie De Backer, and Jolanda van Hengel. 2024. “Three-Dimensional Co-Culturing of Stem Cell-Derived Cardiomyocytes and Cardiac Fibroblasts Reveals a Role for Both Cell Types in Marfan-Related Cardiomyopathy.” MATRIX BIOLOGY 126: 14–24. doi:10.1016/j.matbio.2024.01.003.
- Vancouver
- 1.Aalders J, Léger L, Van der Meeren L, Sinha S, Skirtach A, De Backer J, et al. Three-dimensional co-culturing of stem cell-derived cardiomyocytes and cardiac fibroblasts reveals a role for both cell types in Marfan-related cardiomyopathy. MATRIX BIOLOGY. 2024;126:14–24.
- IEEE
- [1]J. Aalders et al., “Three-dimensional co-culturing of stem cell-derived cardiomyocytes and cardiac fibroblasts reveals a role for both cell types in Marfan-related cardiomyopathy,” MATRIX BIOLOGY, vol. 126, pp. 14–24, 2024.
@article{01HQ0AARBWWFJ3HNEGHZPAZH3D,
abstract = {{Pathogenic variants in the FBN1 gene, which encodes the extracellular matrix protein fibrillin-1, cause Marfan syndrome (MFS), which affects multiple organ systems, including the cardiovascular system. Myocardial dysfunction has been observed in a subset of patients with MFS and in several MFS mouse models. However, there is limited understanding of the intrinsic consequences of FBN1 variants on cardiomyocytes (CMs). To elucidate the CM-specific contribution in Marfan's cardiomyopathy, cardiosphere cultures of CMs and cardiac fibroblasts (CFs) are used. CMs and CFs were derived by human induced pluripotent stem cell (iPSC) differentiation from MFS iPSCs with a pathogenic variant in FBN1 (c.3725G>A; p.Cys1242Tyr) and the corresponding CRISPR-corrected iPSC line (Cor). Cardiospheres containing MFS CMs show decreased FBN1, COL1A2 and GJA1 expression. MFS CMs cultured in cardiospheres have fewer binucleated CMs in comparison with Cor CMs. 13% of MFS CMs in cardiospheres are binucleated and 15% and 16% in cardiospheres that contain co-cultures with respectively MFS CFs and Cor CFs, compared to Cor CMs, that revealed up to 23% binucleation when co-cultured with CFs. The sarcomere length of CMs, as a marker of development, is significantly increased in MFS CMs interacting with Cor CF or MFS CF, as compared to monocultured MFS CMs. Nuclear blebbing was significantly more frequent in MFS CFs, which correlated with increased stiffness of the nuclear area compared to Cor CFs. Our cardiosphere model for Marfan-related cardiomyopathy identified a contribution of CFs in Marfan-related cardiomyopathy and suggests that abnormal early development of CMs may play a role in the disease mechanism.}},
author = {{Aalders, Jeffrey and Léger, Laurens and Van der Meeren, Louis and Sinha, Sanjay and Skirtach, Andre and De Backer, Julie and van Hengel, Jolanda}},
issn = {{0945-053X}},
journal = {{MATRIX BIOLOGY}},
keywords = {{Marfan syndrome,Fibrillin-1,Cardiomyocytes,Cardiac fibroblasts,Disease modelling,Extracellular matrix,NUCLEAR MORPHOLOGY,MATURATION,GENERATION,DIFFERENTIATION,MICROTISSUES,CONNEXIN43,DYNAMICS}},
language = {{eng}},
pages = {{14--24}},
title = {{Three-dimensional co-culturing of stem cell-derived cardiomyocytes and cardiac fibroblasts reveals a role for both cell types in Marfan-related cardiomyopathy}},
url = {{http://doi.org/10.1016/j.matbio.2024.01.003}},
volume = {{126}},
year = {{2024}},
}
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