Influence of Remodeled ECM and Co-culture with iPSC-Derived Cardiac Fibroblasts on the Mechanical Function of Micropatterned iPSC-Derived Cardiomyocytes.
2D cell culture
DIC
Extracellular matrix
Mechanical strain
Microcontact printing
iPSC-Cardiomyocytes
iPSC-Fibroblasts
Journal
Cardiovascular engineering and technology
ISSN: 1869-4098
Titre abrégé: Cardiovasc Eng Technol
Pays: United States
ID NLM: 101531846
Informations de publication
Date de publication:
06 Mar 2024
06 Mar 2024
Historique:
received:
20
12
2022
accepted:
02
01
2024
medline:
7
3
2024
pubmed:
7
3
2024
entrez:
6
3
2024
Statut:
aheadofprint
Résumé
In native heart tissue, functions of cardiac fibroblasts (CFs) include synthesis, remodeling, and degradation of the extracellular matrix (ECM) as well as secreting factors that regulate cardiomyocyte (CM) function. The influence of direct co-culture and CF-derived ECM on CM mechanical function are not fully understood. Here we use an engineered culture platform that provides control over ECM geometry and substrate stiffness to evaluate the influence of iPSC-CFs, and the ECM they produce, on the mechanical function of iPSC-CMs. Mechanical analysis was performed using digital image correlation to quantify maximum contractile strain, spontaneous contraction rate, and full-field organization of the contractions. When cultured alone, iPSC-CFs produce and remodel the ECM into fibers following the underlying 15° chevron patterned ECM. The substrates were decellularized and confirmed to have highly aligned fibers that covered a large fraction of the pattern area before reseeding with iPSC-CMs, alone or in co-culture with iPSC-CFs. When seeded on decellularized ECM, larger maximum contractile strains were observed in the co-culture condition compared to the CM Only condition. No significant difference was found in contractile strain between the Matrigel and decellularized ECM conditions; however, the spontaneous contraction rate was lower in the decellularized ECM condition. A methodology for quantifying alignment of cell contraction across the entire field of view was developed based on trajectories approximating the cell displacements during contraction. Trajectory alignment was unaltered by changes in culture or ECM conditions. These combined observations highlight the important role CFs play in vivo and the need for models that enable a quantitative approach to examine interactions between the CFs and CMs, as well as the interactions of these cells with the ECM.
Identifiants
pubmed: 38448643
doi: 10.1007/s13239-024-00711-8
pii: 10.1007/s13239-024-00711-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Science Foundation
ID : 1648035
Organisme : National Science Foundation
ID : 1648035
Organisme : NHLBI Division of Intramural Research
ID : T32 HL 007936
Organisme : National Institute of Health
ID : U01HL134764
Organisme : National Institute of Health
ID : U01HL134764
Informations de copyright
© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.
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