Biomimetic Model of Contractile Cardiac Tissue with Endothelial Networks Stabilized by Adipose-Derived Stromal/Stem Cells.

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)

Cardiac tissue engineering strategies have the potential to regenerate functional myocardium following myocardial infarction. In this study, we utilized novel electrospun fibrin microfiber sheets of different stiffnesses (50.0 ± 11.2 kPa and 90.0 ± 16.4 kPa) to engineer biomimetic models of vascularized cardiac tissues. We characterized tissue assembly, electrophysiology, and contractility of neonatal rat ventricular cardiomyocytes (NRVCMs) cultured on these sheets. NRVCMs cultured on the softer substrates displayed higher conduction velocities (CVs) and improved electrophysiological properties. Human umbilical vein endothelial cells (HUVECs) formed dense networks on the sheets when co-cultured with human adipose-derived stem/stromal cells (hASCs). To achieve vascularized cardiac tissues, we tested various tri-culture protocols of NRVCM:hASC:HUVEC and found that a ratio of 1,500,000:37,500:150,000 cells/cm 2 enabled the formation of robust endothelial networks while retaining statistically identical electrophysiological characteristics to NRVCM-only cultures. Tri-cultures at this ratio on 90 kPa substrates exhibited average CVs of 14 ± 0.6 cm/s, Action Potential Duration (APD)80 and APD30 of 152 ± 11 ms and 71 ± 6 ms, respectively, and maximum capture rate (MCR) of 3.9 ± 0.7 Hz. These data indicate the significant potential of generating densely packed endothelial networks toge

Evidence level

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

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