Agonistic and antagonistic roles of fibroblasts and cardiomyocytes on viscoelastic stiffening of engineered human myocardium

Publication date: Available online 12 December 2018Source: Progress in Biophysics and Molecular BiologyAuthor(s): Susanne F. Schlick, Florian Spreckelsen, Malte Tiburcy, Lavanya M. Iyer, Tim Meyer, Laura C. Zelarayan, Stefan Luther, Ulrich Parlitz, Wolfram-Hubertus Zimmermann, Florian RehfeldtAbstractCardiomyocyte and stroma cell cross-talk is essential for the formation of collagen-based engineered heart muscle, including engineered human myocardium (EHM). Fibroblasts are a main component of the myocardial stroma. We hypothesize that fibroblasts, by compacting the surrounding collagen network, support the self-organization of cardiomyocytes into a functional syncytium. With a focus on early self-organization processes in EHM, we studied the molecular and biophysical adaptations mediated by defined populations of fibroblasts and embryonic stem cell-derived cardiomyocytes in a collagen type I hydrogel. After a short phase of cell-independent collagen gelation (30 min), tissue compaction was progressively mediated by fibroblasts. Fibroblast-mediated tissue stiffening was attenuated in the presence of cardiomyocytes allowing for the assembly of stably contracting, force-generating EHM within 4 weeks. Comparative RNA-sequencing data corroborated that fibroblasts are particularly sensitive to the tissue compaction process, resulting in the fast activation of transcription profiles, supporting heart muscle development and extracellular matrix synthesis. Large amplitude oscillator...
Source: Progress in Biophysics and Molecular Biology - Category: Molecular Biology Source Type: research