Acellular bioscaffolds redirect cardiac fibroblasts and promote functional tissue repair in rodents and humans with myocardial injury.

Scientific Reports
Daniyil A SvystonyukPaul W M Fedak

Abstract

Coronary heart disease is a leading cause of death. Tissue remodeling and fibrosis results in cardiac pump dysfunction and ischemic heart failure. Cardiac fibroblasts may rebuild damaged tissues when prompted by suitable environmental cues. Here, we use acellular biologic extracellular matrix scaffolds (bioscaffolds) to stimulate pathways of muscle repair and restore tissue function. We show that acellular bioscaffolds with bioinductive properties can redirect cardiac fibroblasts to rebuild microvascular networks and avoid tissue fibrosis. Specifically, when human cardiac fibroblasts are combined with bioactive scaffolds, gene expression is upregulated and paracrine mediators are released that promote vasculogenesis and prevent scarring. We assess these properties in rodents with myocardial infarction and observe bioscaffolds to redirect fibroblasts, reduce tissue fibrosis and prevent maladaptive structural remodeling. Our preclinical data confirms that acellular bioscaffold therapy provides an appropriate microenvironment to stimulate pathways of functional repair. We translate our observations to patients with coronary heart disease by conducting a first-in-human observational cohort study. We show that bioscaffold therapy is...Continue Reading

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Citations

May 20, 2021·Future Cardiology·Vishnu VasanthanPaul Wm Fedak

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Methods Mentioned

BETA
chemical treatments
flow cytometry
biopsy
coronary artery bypass
coronary bypass
biopsies
confocal reflectance microscopy
saturation recovery

Clinical Trials Mentioned

NCT02887768

Software Mentioned

Prism
Ingenuity Pathway Analysis
ADInstruments
GraphPad
Kallisto
Medis Research
MindtheGraph
cvi42
ImageJ

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