Melt electrowritten 3D human cardiac engineered tissues reproduce the enhanced sensitivity of fibrotic patients to doxorubicin Article Swipe
A Sanchez-Bueno
,
Asier Ullate‐Agote
,
Pilar Montero‐Calle
,
José Valdés‐Fernández
,
Eduardo Larequi
,
Ilazki Anaut‐Lusar
,
Patxi San Martín‐Úriz
,
Paula Aguirre‐Ruiz
,
A De La Fuente
,
Luisa Sánchez‐Lorenzo
,
M. Castro
,
Olalla Iglesias‐García
,
Juán José Gavira
,
Felipe Prósper
,
Manuel Mazo
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/eurheartjsupp/suaf083.216
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/eurheartjsupp/suaf083.216
Introduction Cardiotoxicity is a serious and frequent side effect of anthracycline cancer therapy, prompting the cardio-oncologic follow up of patients. However, mechanisms are poorly understood. Moreover, cardiac patients demonstrate an enhance frequency and severity of cardiotoxic events. Purpose In this work we use melt electrowriting (MEW) to generate human induced pluripotent stem cell (hiPSC)-based 3D cardiac tissues to explore this. Methods 3D scaffolds were printed using MEW in medical grade poly-caprolactone. Human iPSCs were differentiated to cardiomyocytes and cardiac fibroblasts using chemically-defined methods, embedded in a fibrinogen precursor and polymerised around the 3D scaffold with thrombin. 3D engineered myocardia were maintaned in vitro an analysed. Results Using a combination of 80% hiPSC-cardiomyocytes and 20% hiPSC-cardiac fibroblasts, we demonstrate that treating MEW-based tissues with clinically-relevant concentrations of the anthracycline doxorubicin recapitulates the main features of cardiac toxicity, including diminished viability and functionality, and severe sarcomeric disarrangement. Moreover, we use TGFβ-treatment to induce a tissue fibrosis, akin to the response in cardiac-diseased patients. Upon treatment with 250 nM doxorubicin, fibrotic MEW-myocardial tissues show significantly worst performance, with decreased viability and functionality as compared with non-TGFβ-treated engineered tissues. Finally, we apply bulk RNAseq, showing how both models faithfully recapitulate the main features of natural human myocardium. Conclusions In summary, we demonstrate that our all-human MEW-based 3D engineered cardiac tissue are able to recapitulate the enhanced clinical cardiotoxicity of cardiac patients in response to anthracycline therapy. Our system is thus posed as an optimal candidate for prophylactic-drug discovery and mechanism deciphering.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/eurheartjsupp/suaf083.216
- https://academic.oup.com/eurheartjsupp/article-pdf/27/Supplement_6/suaf083.216/63902302/suaf083.216.pdf
- OA Status
- bronze
- Related Works
- 10
- OpenAlex ID
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412805599Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/eurheartjsupp/suaf083.216Digital Object Identifier
- Title
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Melt electrowritten 3D human cardiac engineered tissues reproduce the enhanced sensitivity of fibrotic patients to doxorubicinWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-08-01Full publication date if available
- Authors
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A Sanchez-Bueno, Asier Ullate‐Agote, Pilar Montero‐Calle, José Valdés‐Fernández, Eduardo Larequi, Ilazki Anaut‐Lusar, Patxi San Martín‐Úriz, Paula Aguirre‐Ruiz, A De La Fuente, Luisa Sánchez‐Lorenzo, M. Castro, Olalla Iglesias‐García, Juán José Gavira, Felipe Prósper, Manuel MazoList of authors in order
- Landing page
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https://doi.org/10.1093/eurheartjsupp/suaf083.216Publisher landing page
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https://academic.oup.com/eurheartjsupp/article-pdf/27/Supplement_6/suaf083.216/63902302/suaf083.216.pdfDirect link to full text PDF
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YesWhether a free full text is available
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bronzeOpen access status per OpenAlex
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https://academic.oup.com/eurheartjsupp/article-pdf/27/Supplement_6/suaf083.216/63902302/suaf083.216.pdfDirect OA link when available
- Concepts
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Medicine, Doxorubicin, Sensitivity (control systems), Fibrosis, Cancer research, Pathology, Cardiology, Biomedical engineering, Internal medicine, Chemotherapy, Engineering, Electronic engineeringTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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