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journal article·2024-02-12Open access

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

Laura Paz-Artigas, Sandra González-Lana, Nicolás Polo, Pedro Vicente, Pilar Montero-Calle, Miguel A. Martínez, Gregorio Rábago, Margarida Serra, Felipe Prósper, Manuel M. Mazo, Arantxa González, Ignacio Ochoa, Jesús Ciriza

ACS Biomaterials Science & Engineering· Volume 10· Issue 2
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Source abstract

Abstract

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.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Pluripotent Stem Cells Research · 3D Printing in Biomedical Research · Tissue Engineering and Regenerative Medicine

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Tissue Microenvironment (TME) Lab, Aragón Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza 50018, Spain

Institute for Health Research Aragón (IIS Aragón), Zaragoza 50009, Spain

BEONCHIP S.L., CEMINEM, Campus Río Ebro, Zaragoza 50018, Spain

Instituto de Biologia Experimental e Tecnológica (iBET), Oeiras 2780-157, Portugal

Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras 2780-157, Portugal

Cardiology and Cardiac Surgery Department, Clínica Universidad de Navarra, Pamplona 31009, Spain

CIBER-BBN, ISCIII, Zaragoza 50018, Spain

Regenerative Medicine Program, Cima Universidad de Navarra, and Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona 31008, Spain

Hematology and Cell Therapy, Clínica Universidad de Navarra, and Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona 31008, Spain

CIBERONC, Instituto de Salud Carlos III, Madrid 28029, Spain

Program of Cardiovascular Diseases, CIMA Universidad de Navarra, and Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona 31008, Spain

CIBERCV, Instituto de Salud Carlos III, Madrid 28029, Spain

Funding

Gobierno de Arag?n · Ministerio de Ciencia e Innovaci?n · European Regional Development Fund · Gobierno de Navarra · Horizon 2020 Framework Programme

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