132268 20260217205506.0 doi 10.1021/acsbiomaterials.3c01302 sideral 137431 ART-2024-137431 eng Paz-Artigas, Laura Universidad de Zaragoza (orcid)0000-0001-6139-5905 Generation of Self-Induced Myocardial Ischemia in Large-Sized Cardiac Spheroids without Alteration of Environmental Conditions Recreates Fibrotic Remodeling and Tissue Stiffening Revealed by Constriction Assays 2024 Access copy available to the general public Unrestricted A combination of human-induced pluripotent stem cells (hiPSCs) and 3D microtissue culture techniques allows the generation of models that recapitulate the cardiac microenvironment for preclinical research of new treatments. In particular, spheroids represent the simplest approach to culture cells in 3D and generate gradients of cellular access to the media, mimicking the effects of an ischemic event. However, previous models required incubation under low oxygen conditions or deprived nutrient media to recreate ischemia. Here, we describe the generation of large spheroids (i.e., larger than 500 μm diameter) that self-induce an ischemic core. Spheroids were generated by coculture of cardiomyocytes derived from hiPSCs (hiPSC-CMs) and primary human cardiac fibroblast (hCF). In the proper medium, cells formed aggregates that generated an ischemic core 2 days after seeding. Spheroids also showed spontaneous cellular reorganization after 10 days, with hiPSC-CMs located at the center and surrounded by hCFs. This led to an increase in microtissue stiffness, characterized by the implementation of a constriction assay. All in all, these phenomena are hints of the fibrotic tissue remodeling secondary to a cardiac ischemic event, thus demonstrating the suitability of these spheroids for the modeling of human cardiac ischemia and its potential application for new treatments and drug research. info:eu-repo/grantAgreement/EC/H2020/778354/EU/Heart On chip based on induced pluripotent Stem cell Technology for personalized Medicine/CISTEM This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 778354-CISTEM info:eu-repo/grantAgreement/EC/H2020/829010/EU/Advanced and versatile PRInting platform for the next generation of active Microfluidic dEvices/PRIME This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 829010-PRIME info:eu-repo/grantAgreement/EC/H2020/848109/EU/MiCrovasculaR rarefaction in vascUlar Cognitive Impairement and heArt faiLure/CRUCIAL This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 848109-CRUCIAL info:eu-repo/grantAgreement/EC/H2020/874827/EU/Computational biomechanics and bioengineering 3D printing to develop a personalized regenerative biological ventricular assist device to provide lasting functional support to damaged hearts/BRAV3 This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 874827-BRAV3 info:eu-repo/grantAgreement/ES/ISCIII CB16-11-00483 info:eu-repo/grantAgreement/ES/ISCIII/PI19-01350 info:eu-repo/grantAgreement/ES/ISCIII/PI21-00946 info:eu-repo/grantAgreement/ES/MCIN/PLEC2021-008127 info:eu-repo/grantAgreement/ES/MCINN/PID2022-139859OB-I00 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es 5.5 2024 MATERIALS SCIENCE, BIOMATERIALS 20 / 55 = 0.364 2024 Q2 T2 1.105 2024 Biomedical Engineering 2024 Q1 Biomaterials 2024 Q2 9.7 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion González-Lana, Sandra Polo, Nicolás Vicente, Pedro Montero-Calle, Pilar Martínez, Miguel A. Universidad de Zaragoza (orcid)0000-0002-8375-0354 Rábago, Gregorio Serra, Margarida Prósper, Felipe Mazo, Manuel M. González, Arantxa Ochoa, Ignacio Universidad de Zaragoza (orcid)0000-0003-2410-5678 Ciriza, Jesús Universidad de Zaragoza (orcid)0000-0002-8666-622X 1003 443 Universidad de Zaragoza Dpto. Anatom.Histolog.Humanas Area Histología 5004 605 Universidad de Zaragoza Dpto. Ingeniería Mecánica Área Mec.Med.Cont. y Teor.Est. 10, 2 (2024), 987-997 ACS biomater. sci. eng. ACS BIOMATERIALS SCIENCE & ENGINEERING 2373-9878 12544963 http://zaguan.unizar.es/record/132268/files/texto_completo.pdf Versión publicada 3228414 http://zaguan.unizar.es/record/132268/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:132268 articulos driver 2026-02-17-20:23:36 ARTICLE