3-D biomechanics and epigenomics reveal atypical fibroblast responses in cardiometabolic disease.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Cell behavior is influenced by substrate stiffness and cell-cell and cell-environment interactions. The limitations of two-dimensional (2-D) culture, such as its inability to fully capture the complexity of cell interactions and tissue structure, highlight the necessity of three-dimensional (3-D) cell culture. This explicitly applies to "disease modeling in a dish" platforms for translational studies. 3-D bioprinting demonstrates significant potential in recapitulating the intricate physiological environments of human tissues in both healthy and pathological states. With the alarming rise in obesity, addressing systemic pathophysiological dysfunction beyond adipose tissue itself, such as the heart, is inevitable. To capture cellular and tissue-level responses to overnutrition, we used state-of-the-art 3-D bioprinting technology to understand the acute response of 3-D matrix-embedded human cardiac fibroblasts to a "high-fat diet" mimic. Chromatin accessibility profiling revealed that excess fatty acid (FA) exposure in 2-D induces a noncanonical extracellular matrix gene program that is minimally expressed in healthy adult myocardium. In contrast, 3-D cultures exhibited reduced fibroblast proliferation and blunted transcriptional responses to the impact of biomechanical cues under metabolic stress, reflecting a more quiescent and physiologically relevant phenotype. Furthermore, w

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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