Engineering stem cell cardiac patch with microvascular features representative of native myocardium

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cardiovascular Research

Background:

• The native myocardium features highly aligned tissue and vasculature for optimal function.
• Current strategies for engineering cardiac tissue lack ideal biomaterials and effective vascularization for clinical applications.
• Developing oriented, high-density microvessels is essential for cardiovascular therapies.

Purpose of the Study:

• To create an oriented, dense microvessel network mimicking physiological myocardial microvascular features.
• To investigate the role of extracellular matrix (ECM) topography in guiding neovascularization.
• To enhance microvascular network formation using co-cultures of human mesenchymal stem cells (hMSCs) and endothelial cells (ECs).

Main Methods:

• Utilized highly aligned decellularized human dermal fibroblast sheets as ECM scaffolds.
• Co-cultured hMSCs and endothelial cells (ECs) on aligned and randomly organized ECM scaffolds.
• Investigated the influence of topographical features on cell interactions and neovasculature formation.

Main Results:

• Aligned ECM topography, translated via CD166, significantly enhanced hMSC-EC crosstalk and vascular network formation.
• Aligned ECM nanofibers promoted superior structure, length, and density of microvascular networks compared to random scaffolds.
• hMSC-EC co-culture stimulated pro-angiogenic factors and matrix remodeling, achieving native myocardium-like intercapillary distance (20 μm).

Conclusions:

• Co-culture of hMSCs and ECs on aligned ECM scaffolds generates physiologically oriented and dense microvascular networks.
• This approach shows significant potential for advancing cardiac tissue engineering.
• The study highlights the importance of topographical cues in biomaterials for vascular regeneration.