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Stromal Cells in Dense Collagen Promote Cardiomyocyte and Microvascular Patterning in Engineered Human Heart Tissue.
Meredith A Roberts1,2,3, Dominic Tran1, Kareen L K Coulombe2,3,4
11 Department of Bioengineering, University of Washington , Seattle, Washington.
Tissue Engineering. Part A
|March 10, 2016
Summary
Engineered heart tissue with patterned microvasculature was created using high-density collagen and stromal cells. This approach enables functional cardiac tissue with electrical synchronization and vascular patency for regeneration and disease modeling.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Cardiovascular Research
Background:
- Current cardiac tissue engineering struggles to integrate contractile tissue with perfusable vasculature.
- Achieving both aligned contractile tissue and functional microvasculature in engineered constructs remains a significant challenge.
Purpose of the Study:
- To develop a method for incorporating patterned microvasculature into engineered heart tissue.
- To overcome the limitations of low-density gels for vascularization and high-density gels for cardiomyocyte function.
Main Methods:
- Utilized high-density collagen hydrogels (≥6 mg/mL) to support patterned microvasculature.
- Co-cultured human embryonic stem cell-derived cardiomyocytes (hESC-CMs) with matrix remodeling stromal cells in dense collagen.
- Assessed tissue contraction, electrical pacing, vascular network patency, and cardiomyocyte electrical synchronization.
Main Results:
- Co-culture with stromal cells enabled hESC-CMs to structurally mature and form anisotropic constructs in high-density collagen.
- Engineered cardiac constructs exhibited measurable active contractions (0.1 mN/mm²) and could be paced up to 2 Hz.
- Patterned microvascular networks remained patent for 2 weeks, and hESC-CMs demonstrated electrical synchronization.
Conclusions:
- Successfully incorporated patterned microvasculature into functional engineered heart tissue by co-culturing hESC-CMs with stromal cells in dense collagen.
- This approach balances the need for cardiomyocyte contractility and vascular structural support.
- Enables the generation of more complex engineered tissues for myocardial regeneration and cardiac disease modeling.
